Introduction: Dust mites are considered one of the main sources of aeroallergens and are associated with the development of allergic diseases. Recurring contact with the allergen can lead to chronic inflammation, which may result in the onset of allergic diseases such as asthma, rhinitis and atopic dermatites. In Brazil, the most prevalent mites belong to the genera Dermatophagoides and Blomia. However, in a previous study conducted by our group we identified for the first time the presence of the mite Glycycometus malaysiensis, which had already been reported as a sensitizing agent in Asian countries. Both G. malaysiensis and B. tropicalis mites exhibit morphological similarities, raising the possibility of cross-reactivity between their allergens. Nevertheless, the specific allergens of this mite species have not been fully characterized. Objectives: Identification and isolation of the mite G.malaysiensis from house dust and evaluation of antigen reactivity in serum from atopic patients. Material and Methods: The allergenic extracts were identified using the multiplex PCR technique and characterized using SDS-PAGE and Western Blot. A total of 57 sera from atopic patients had IgE reactivity to these extracts assessed by indirect ELISA. Results: Using Western blots without inhibition and with inhibition to the extract of D. pteronyssinus, was observed a positive reactivity of the atopic patients to the bands referring to the G. malaysiensis mite. In addition, the patients tested showed greater IgE reactivity to the extracts identified with the D. pteronyssinus and G. malaysiensis mites compared to the extract containing only the D. pteronyssinus mite. Conclusions: In this study, we could observe the immunogenic potential of G. malaysiensis and its possible significance in the evaluated indiviudals.

The phenomenon of dysbiosis in the intestinal microbiome can influence the host's immune development and the incidence of allergic diseases. It is believed that microbiome-host interactions, i.e., symbiosis, contribute to the proper development of the immune system, while microbial dysbiosis has been associated with a variety of inflammatory disorders, including asthma. The aim of this study is to characterize the taxonomic profile of the intestinal microbiota in asthmatic individuals participating in the World Asthma Phenotypes (WASP) and associate it with related immunomodulatory mechanisms. The assessment of the intestinal microbiota was conducted through sequencing the V4 region of the 16S rRNA gene from bacterial DNA extracted from stool samples, followed by bioinformatic analysis using the QIIME2 software. Association with the immune response was investigated using markers such as skin prick test positivity, induced sputum cellularity, and cytokine levels in nasal lavage. Although all predominant phyla, such as Tenericutes, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, were consistent between asthmatics and non-asthmatics, differences in relative abundances were observed. No significant differences in bacterial richness or diversity were identified between asthmatics and non-asthmatics based on alpha diversity. However, a statistically significant dissimilarity in beta diversity was observed. The genus Bacteroides was the most abundant, contributing to the dissimilarity within the asthmatic group, while Prevotella was more prevalent in non-asthmatics. The presence of Bacteroides in the microbiota of asthmatics correlated with IL-4 production in nasal lavage. These results reinforce the understanding of differences in the microbial community between asthmatic and non-asthmatic individuals.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a potentially fatal complication of SARS-CoV-2 infection. It is a post-infectious condition, whose symptoms and laboratory findings demonstrate systemic hyperinflammation. There are still many doubts about risk factors, ideal management and different clinical courses, but studies have been developed to unravel the genetics of the syndrome's susceptibility. Ain: To identify genetic variants that are determinant for MIS-C. Methods: This is a case series study of patients with no prior health conditions, diagnosed with MIS-C in Brazil. Clinical and laboratory data were collected from medical records, as well as patient cells to perform exome sequencing. The prioritization of variants was carried out focusing on 126 human genes that encode proteins involved in the mechanisms by which SARS-CoV-2 modulates the immune response, from a list available in the Reactome database. For ancestry analysis, it was used the 1000 Genomes Project and genetic data from BR-MIS-C as a reference, using autosomal variants with MAF > 0.1 common to both. We have considered Europeans, Africans and Native Americans as forming groups of the Brazilian population. For functional analysis, the amino acid sequences, structure and functional domains of IL- 17RC, IFNA10 and NLRP12 were obtained and the evolutionary conservation of amino acid positions was evaluated. Results: A total of 21 patients with MIS-C was enrolled in this study; of these, 62% (n=13) were male and 67% (n=14) were declared as mixed race. The median age was 8 years (IQR, 5-12). In addition to fever, observed in 100% of patients, the most prevalent symptoms were abdominal pain (74%, n=15), followed by skin rash (57%, n=12) and dyspnea (57%, n=12). The main outcome observed was shock (48%). By  analyzing the prioritization of coding variants in genes that participate of the SARS-CoV-2 infection process, we identified rare deleterious variants potentially involved in the development of MIS-C in 38% (n=8) of the individuals studied. Five out of twenty one (24%) patients had functional mutations in the NLRP12 gene, located at 19q13.42, which encodes a cytoplasmic protein involved in the suppression of inflammatory responses in activated monocytes. We also identified three mutations in the IL17RC gene, located on chromosome 3p25.3, which encodes one of the IL-17 receptor chains, and also a nonsense variant in the IFNA10 gene, located in the gene cluster at locus 9p21.3, which encodes the IFN-α10 factor and has great deleterious potential. Ancestry analysis revealed an admixed pattern of Brazilian children with MIS-C, ranging from 0.77 European ancestry (P7) to 0.78 African ancestry (P1). Variants in IL17RC, IFNA10 and NLPR12 were more frequently inherited from Europeans. Evaluation of evolutionary conservation of amino acids revealed intermediate to high degree of conservation for amino acid positions in IL-17RC, IFNA10 and NLRP12. Conclusion: Rare and deleterious mutations in coding regions of the NLRP12, IL17RC and IFNA10 genes may contribute to the occurrence of MIS-C. 

The objective of the present study is to evaluate changes in cells and tissues that make up the colonic wall of rats inoculated with oocysts of T. gondii (strain RH, genotype I) and immunostimulated with 100 mg/kg of E. purpurea (L.) Moench. Twenty-four male Rattus norvegicus were randomly divided into four groups (n=6),
namely: control group (CG); group infected with 500 T. gondii oocysts and not immunostimulated (GI); control group immunostimulated with 100 mg/kg of E. purpurea (GC+EP); and group infected and immunostimulated with 100 mg/kg of E. purpurea (GI+EP). The experimental protocol (nº 7633021018) was approved by the Ethics Committee for the use of experimental animals. Twenty-eight days after inoculation, at 93 days of age, the rats were euthanized. The colon of each was collected, fixed and analyzed using histochemical and immunohistochemical techniques. Toxoplasmic infection, as well as immunostimulation with 100 mg/kg of E. purpurea, caused histomorphometric alterations, increase in the distribution of total mast cells and mast cells and enterochromaffin cells that express 5-HT and in theproportion of intraepithelial lymphocytes in the colon of rats. We demonstrated that there was an increase in all goblet cell phenotypes evaluated in the colonic mucosal epithelium. In addition, we demonstrated that the infection caused histopathological hanges to the colon wall which were attenuated by immunostimulation with 100 mg/kg of E. purpurea. Taken together, our results suggest that part of the changes in cells and tissues that make up the colonic wall were attenuated by immunostimulation with 100 mg/kg of E. purpurea (L.) Moench, suggesting that it can be used in the future as an adjunct to conventional treatment; however, for that, new studies are necessary. 

COVID-19 is characterized by a wide spectrum of clinical manifestations and immune responses can determine unfavorable outcomes during the course of SARS-CoV-2 infection. Some minority ethnic groups seem to be more vulnerable to infection or to present severe clinical conditions, whether due to biological or sociodemographic factors. There are few data related to genomic ancestry and clinical outcomes of the disease, for this reason, this study aimed to estimate the ancestral profile by means of Ancestry Informative Markers (AIMs) and to evaluate the hematological and lymphocyte profile of individuals with COVID-19 from from the cities of Salvador-Ba and Feira de Santana-Ba. 58 individuals with COVID-19 classified into mild and severe clinical conditions were analyzed. Genotyping was performed using PCR and the lymphocyte profile was identified using immunophenotyping. Regarding the ancestral profile, the severe group presented 40.2%, 30.4% and 29.4% of European, African and Amerindian ancestry profiles, respectively. While the light group had 44.8%, 30.9% and 24.3% of European, Amerindian and African profile, respectively. The severe group presented: increase in total leukocytes and neutrophils; reduction in the parameters of erythrocytes, hemoglobin, hematocrit and lymphocytes in comparison with the mild group, as well as a decrease in the cell profiles of TCD4+, TCD8+ and B lymphocytes. with data describing that the individual's immune response may play a crucial role in the pathogenesis of the disease.

INTRODUCTION: COVID-19, a disease caused by the SARS-COV-2 virus, can progress to

severe cases and promote Acute Respiratory Distress Syndrome (ARDS). The pathophysiology of severe COVID is not well understood, but it appears to be related to endothelial dysfunction combined with a dysregulated immune response and cytokine storm. COVID-19 evolves quickly into severe cases, so it is of great importance to evaluate laboratory tests and biomarkers that are indicators of the host's immune response that are effective in predicting the evolution of severe cases, with the aim of optimizing clinical and therapeutic management to avoid adverse outcomes. unfavorable events, such as death. OBJECTIVE: To evaluate the expression of the ARG1, NOS2, ITGA4 and SELPLG genes in total leukocytes and to measure the levels of P-selectin and PSGL-1 proteins in the plasma of patients with COVID-19, associating it with the severity of the clinical picture and the prognosis of the disease . METHODOLOGY: In the present controlled observational study approved by CONEP (Opinion No.: 4,014,165) we recruited 117 patients with a confirmed diagnosis of COVID-19 (severe = 58 and mild = 59). Demographic, clinical, and laboratory parameters were collected at study admission. We used the RT-qPCR assay to measure the relative expression of genes. We evaluated plasmatic levels of P-selectin and PSGL-1 with ELISA assay. RESULTS: we found that men, elderly people with pre-existing comorbidities (p<0.0001) were more likely to have a severe outcome. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) (p<0.0001) were altered in the severe group. Patients with severe symptoms exhibit increased expression of the ARG1 (p=0.032) and SELPLG (p<0.0001) genes, as well as higher plasma concentrations of P-selectin (p=0.031) and PSGL-1 (p<0.002) proteins. CONCLUSION: Our data suggest that laboratory tests such as RNL, RPL, elevated expression of SELPLG / ARG1 genes in leukocytes and increased levels of P-selectin and PSGL-1 in plasma, may be potential useful diagnostic and prognostic biomarkers for severe disease, guiding strategic treatment for COVID-19.

In several areas of Latin America, the geographic distribution of cutaneous leishmaniasis (CL) overlaps with areas of Chagas disease transmission ranging from 12 to 70% of patients with clinical symptoms of leishmaniasis. Studies show a difference in the expression of T cells in CL and in patients coinfected with Trypanosoma cruzi in relation to patients with isolated Leishmania. The aim of this study is to investigate whether the immune response of patients with CL caused by L. braziliensis and coinfected with T. cruzi is associated with the clinical course of leishmaniasis. A case-control study was carried out with one hundred and eighty sera from patients with CL caused by L. braziliensis, where chimeric proteins specific to Trypanosoma cruzi were used to detect coinfection with Chagas disease. We identified 20 patients with CL who were coinfected with T.cruzi, all of whom had higher anti-Leishmania antibody titers than patients infected with Leishmania alone. As for the production of cytokines, IL-6 was the one with the highest levels in the group of co-infected patients compared to the group with leishmaniasis alone. There was no statistical difference in the production of IFN-γ, TNF, IL-1β between patients coinfected with Leishmania braziliensis and T.cruzi. With regard to clinical outcome, fourteen (70%) of the co-infected patients failed antimonial therapy, and of patients with Leishmania infection alone, a total of sixty-two (42%) failed. These results indicate that co-infection can interfere with the immune response and influence the response to treatment of patients with CL caused by L. braziliensis. 

Introdução: A sepse é uma condição clínica com elevado risco de morte, definida como uma disfunção orgânica decorrente de uma resposta desregulada do hospedeiro à infecção, sendo a disfunção cardíaca uma das principais complicações dos pacientes com sepse e está intimamente associada à elevada mortalidade induzida por esta condição clínica. Atualmente, a incidência e a mortalidade da sepse ainda são elevadas, apontando a importância  do uso de biomarcadores no diagnóstico precoce e no seu prognóstico. Nesse cenário, os microRNA surgem como candidatos potenciais com alta especificidade e sensibilidade para a sepse. Diante desse contexto, o presente estudo visou investigar o perfil de expressão dos miRNA e sua correlação com as vias intracelulares envolvidas no remodelamento do miocárdio decorrente da sepse. Métodos &amp; Resultados : O levantamento dos transcriptomas publicamente disponíveis em NCBI, GEO e ENA, resultou na obtenção do conjunto de dados GSE171546. Este conjunto dispõe de 20 amostras : 5 compondo o grupo controle e 15 amostras constituindo o grupo com cardiomiopatia séptica, separadas nos intervalos de tempo: 24h, 48h e 72h. A importação e análise desse conjunto de dados foram feitas a partir da plataforma online do Galaxy. Foi então avaliado o valor de p &lt;0,05 e Fold change para encontrar os Genes Diferencialmente Expressos (GDE) e microRNA Diferencialmente Expressos (MDE). A partir desta análise, 768 GDE foram encontrados no período de 24h, 312 no grupo 48h e 255 GDE no
intervalo de 72h, além de dois MDE (miR-8110 e miR-574-5p). As análises de
enriquecimento de vias e de ontologia genética foram feitas pelo Webgestalt. A
verificação dos mRNA alvos dos MDE foi realizado através do Mirwalk e
posterior construção de rede de interação entre GDE e MDE, no Cytoscape.
Conclusão : Os dois miRNA identificados estão relacionados a diversas vias
intracelulares envolvidas no remodelamento do miocárdio associado à
disfunção cardíaca decorrente da sepse e estão diferencialmente modulados
no transcriptoma analisado neste estudo, sugerindo um papel relevante como
potenciais biomarcadores de prognóstico da cardiomiopatia decorrente da
sepse.

COVID-19 is an acute respiratory illness caused by the new coronavirus (SARS-CoV-2). Although most cases are asymptomatic or have mild symptoms, about 20% of those affected by the disease develop its severe form. The progression of COVID-19 has been associated with hypoxia, systemic physiological dysregulation and coagulopathies, but the risk factors for its evolution to the severe form are not yet fully understood. The poor prognosis of the disease seems to be associated with factors involved in the virus-host interaction, such as impaired IFN type I signaling –the main innate line of defense for mounting an effective antiviral immune response –associated with dysregulated expression of the pro-inflammation cytokine. Furthermore, human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, appear to be reactivated in response to infectious agents such as SARS-CoV-2, modulating the innate immune response and leading to various deleterious systemic effects, but with a role the worsening of COVID-19 are still incipient.This study analyzed gene expression and plasma levels of some molecules identified as markers of COVID-19 severity, comparing mild and severe disease. We evaluated 71 individuals (46 mild and 25 severe cases) for gene expression analysis, and 139 for plasma cytokine dosage (58 mild and 81 severe cases). Expressions of IFN genes and their receptors (INFAR1 and INFAR2), IL-17 and HERVs were analyzed in both groups, as well as IL-2, CCL2 and CCL3 cytokines. The INFAR2 gene and the IL-2 cytokine were higher in the mild group, while CCL3 chemokine levels were more significant inthe severe group. These findings add to the evidence of how the dynamics of the host's immune response can impact the clinical outcome of SARS-CoV-2 infection.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is a global crisis. Brazil is the second country with the highest number of deaths due to COVID-19 in the world, 701,494 deaths. Many factors can determine the severity of COVID-19, including viral load, genetic factors, presence of comorbidities, age, gender, and uncontrolled inflammation. It is estimated that approximately 5% of cases develop severe acute respiratory distress syndrome due to cytokine storm. A cell signaling pathway that may be involved in this process is PI3K/AKT/MTOR. Studies demonstrate that AKT inhibition can potentially suppress pathologic inflammation, cytokine storm, fibroproliferation, and platelet activation associated with COVID-19. Objectives: To investigate the association between AKT1 gene variants and the severity of COVID-19. Methods: Peripheral blood samples and sociodemographic data were collected from 508 individuals with COVID-19, 216 mild cases and 292 severe cases, from April 2020 to April 2021. Plasma cytokine concentrations were measured by ELISA. Genotyping of the SNPs, rs1130214 and rs2494746, and AKT1 gene expression were performed using Thermo Fisher kits and analyzed by qRT-PCR in the QuantStudio 12K (Applied Biosystems). Results and Conclusions: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. Meanwhile, the C allele of rs1130214 was associated with elevated TNF-α and D-dimer levels. In addition, variants demonstrated a cumulative risk associated with severity, criticality, and death from COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Therefore, the present study contributes to understanding the influence of the AKT1 gene and its variants on immune damage in individuals infected with SARS-CoV-2, which may be useful in the future to help predict a worse outcome of COVID-19.

Ophidian accidents are a major public health problem in tropical regions of the world, due to the large number of people affected and the risk of morbidity and mortality after envenoming. In Bahia approximately 70% of the accidents are caused by the species Bothrops leucurus. Snake venoms are a complex mixture of organic and inorganic substances that change between species and according to factors such as evolutionary development, geographical, dietary and biological variations, which reinforces the need to investigate the mechanisms involved in the actions of each venom. Local manifestations triggered by envenoming, such as persistent inflammation, tissue damage and myonecrosis, are inefficiently neutralized and irreversible tissue damage may result. Coadjuvant therapies are proposed to reduce the local damage of bothropic envenoming, however there is still no alternative therapy applied in the clinic. G-CSF treatments have been used in the functional and structural recovery of injured muscles. The aim of this study was to characterize the temporal profile of injury and repair induced by B. leucurus venom envenomation, as well as the degree of structural impairment of skeletal muscle, the profile of inflammatory cells and cytokines released after venom inoculation, and to evaluate the effect of treatment with G-CSF on envenoming skeletal muscle in an experimental model. For this, Swiss mice were inoculated with 50 μg/mL of B. leucurus venom and euthanized in the experimental periods of 3 h, 6h and 24 h, 7 d, 14 d and 28 d. Animals inoculated with B. leucurus venom were treated with G-CSF for two consecutive days after completing 7 d and 28 d of envenomation. Serum and muscle samples were collected, processed and used to assess the myotoxic activity of the venom, through plasma CK dosage, histopathological analysis of muscle lesions and quantification of inflammatory cells and cytokine gene expression by RT-qPCR. CK results demonstrated peak release after 6 h. Histological sections stained with HE showed inflammatory infiltrate in all analyzed periods, with predominance of the concentration in 7 d and 14 d; presence of ‘delta lesion’, oedema, hemorrhage, myonecrosis and myofibrillar hypercontraction. The evaluation of cytokine gene expression showed an increase in TNF-α, IL-1β, INFy, IL-6, IL-10, ARG and VEGF at the different times analyzed. In general, the treatment with G-CSF had an immunomodulatory action on the inflammatory process, altering the expression of cytokines, but not in the histological evaluation, indicating the possibility of a positive development in the treatment with G-CSF for skeletal muscle injuries caused by envenoming by B. leucurus, using a different treatment protocol. 

Introduction: COVID-19 has brought complications to various countries. In Brazil, the spread of the infection generally moved from state capitals to interior cities. This pattern was also identified in Bahia, making it important to trace the level of viral circulation and the impact of the infection in the regions of the state. Objective: To investigate the relationship between the seroprevalence of SARS-CoV-2 infection in blood donor samples and the notification of virus infection cases in the Interior of Bahia in 2020. Materials and Methods: The population sample originally consisted of 6,877 blood donors in 13 cities, located in four regions of the state of Bahia (north, south, east, and west). Subsequently, serum samples were tested for the detection of anti-SARS-CoV-2 antibodies using the TR COVID-19 IGM/IGG Kit – Bio-Manguinhos. Statistical analyses were conducted to estimate the crude seroprevalence of the infection and a Bayesian correction method was used to determine the seroprevalence adjusted by region of the state. The data on notification/incidence are sourced from the public database of the Secretary of Health of the State of Bahia (SESAB) and DATASUS. Only records marked as "POSITIVE" and "SRAG for COVID-19" in the year 2020, between April and November, were preserved. Results: The blood donors had a median age of 34 years (IQR: 25-42). Most of the tested donors were from the western region of Bahia. The seroprevalence among blood donors and the cumulative incidence of infection/hospitalization between April and November 2020 were 12.2% and 5.0%, respectively. Differences were identified between the seroprevalence of blood donors and the accumulated incidence of cases, mainly in the west and east regions of Bahia, in November 2020. Conclusion: This study reveals a discrepancy between the seroprevalence of SARS-CoV-2 in blood donors and the reported cases of infection in Bahia in 2020, particularly in the western and eastern regions of the state. The prevalence of 12.2% among blood donors, compared to the cumulative incidence of 5.0% of infections/hospitalizations, suggests substantial underreporting of COVID-19 cases. The research contributes to a better understanding of the dynamics of SARS-CoV-2 infection in the interior of Bahia, providing valuable data for planning more targeted and efficient public health strategies to contain the virus's spread, especially in less accessible areas and among vulnerable populations.

Introduction: Traumatic Brain Injury (TBI) is a complex and multifactorial pathology, being a major cause of death and disability for humans. Immediately after TBI, astrocytes and microglia react with complex morphological and functional changes known as reactive gliosis and forms, in the area immediately adjacent to the lesion, the glial scar, the major barrier to neuronal regeneration in the central nervous system. The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis leaves, has been shown to have neurogenic, neuroprotective, and anti-inflammatory effects, demonstrated in in vitro models of glutamate-induced toxicity, neuroinflammation, and demyelination. The present study investigated, the effect of agathisflavone in neuronal integrity and in the modulation of gliosis in ex vivo models of TBI. Methodology: Microdissections from the encephalon of Wistar rats (P6-8), were prepared and subjected to mechanical injury (MI) and treated or not daily with agathisflavone (5 μM) for 3 days. Astrocyte reactivity was investigated by measuring mRNA and expression of GFAP protein in the lesioned area by immunofluorecence and westernblot; proportion of microglia was determined by immunofluorescence for Iba-1; mRNA expression for inflammasome NRPL3 and interleukin -1 beta (IL-1β) was determined by RT-qPCR. Results: It was observed that lesion of the cortical tissue induced astrocytes over expressing GFAP in the typical glial scar formed, and agathisflavone modulated GFAP expression at transcriptional and pos-transcriptional level associated with reduction of glial scar. MI induced increase in the proportion of microglia (Iba-1+) that was not observed in agathisflavone treated cultures. Moreover, the flavonoid modulated negatively both NRLP3 and IL-1β mRNA expression that was increases in the lesioned area of the tissue. Conclusion: All of these findings reiterate the regulatory property of the inflammatory response of glial cells by the flavonoid agathisflavone, which can impact in neuroprotection and should be considered for future pre-clinical and clinical studies for CNS pathologies, including TBI. 

HTLV infection establishes a low proviral load since the spread of the virus occurs by virological synapse and by mitotic multiplication of infected cells. The clonal expansion of infected cells, in addition to being important for latency of infection, seems to lead to dysfunctions in the host's immune system, generating autoimmunity (HAM/TSP, uveitis and cardiovascular diseases) and malignancy (ATL). The impairment of the immune system caused by HTLV-1/2 infection makes the infected individual susceptible to other infectious diseases such as tuberculosis and Acquired Immunodeficiency Syndrome (AIDS). HIV and HTLV have similar genomic organization and tropism for cells of the immune system (CD4+ T cells). However, the influence of HTLV-1/2 on the progression of the pathology developed by HIV has been widely discussed. This work intends, through flow cytometry, to identify the intracytoplasmic infection of cells infected by HTLV and in coinfected patients, demonstrating the participation of the immune system in both patients. 14 individuals monoinfected by HTLV-1 and 15 individuals coinfected by HTLV-1/HIV-1 participated in the research. Detection of intracellular HTLV-1 infection was performed by labeling anti-CD4 monoclonal antibodies and a mix of probes complementary to an HTLV-1 LTR domain to target proteins in cells. Infected cells were identified by flow cytometry and statistically analyzed. At the end of the study, it was found that the anti-HTLV probe mix was able to identify infected cells in different cell types, in mono or co-infection. A smaller number of CD4+ monocytes was observed in co-infected individuals, as well as in patients using ART. When evaluating the phenotypic profile of cellular activation, a trend towards a decrease in the expression of HLA-DR and an increase in the expression of CTLA-4 was observed in monoinfected individuals with clinical manifestations associated with HTLV-1. It is suggested that the presented methodology be used as a tool in the definition of infected cell populations in patients with HTLV-1, which would open new possibilities for monitoring and therapeutic definition in these individuals.

Acute lymphocytic leukemia (ALL) has a bimodal incidence, characterized by loss of normal ability to differentiate and proliferate, with an accumulation of lymphoid progenitor cells and clonal expansion in bone marrow, peripheral blood, and other tissues. It is the most common in childhood and adolescence, with several factors associated with its etiology. The use of flow cytometry, in conjunction with morphological analysis, is essential for the diagnosis and followup of such diseases. In this context, the analysis of the expression of molecules in the maturation curve of normal and neoplastic lymphoid precursors is a tool that contributes to elucidating the behavior of the medullary environment in the analysis of Measurable Residual Disease (MRD). The endoglin molecule (ENG, CD105) is a co-receptor of the TGF-β family that plays a crucial role in the regulation of angiogenesis. Although best known for its expression in endothelial cells, endoglin is also expressed in hematopoietic stem cells (HSC) and has recently been suggested as a marker of poor prognosis for pediatric patients with B Cell Precursor ALL (BCP-ALL). In this context, the present work evaluated the expression of CD105 in normal precursors of B cells, also called hematogonia, and in leukemic blasts from pediatric patients with BCP-ALL. The study was carried out on onco-pediatric patients samples from Hospital Aristides Maltez, Martagão Gesteira, and Santa Casa de Itabuna, using pre-defined panels for the analysis of CD105 expression. Events were acquired using a BD FACSCalibur flow cytometer and analyzes were performed using the Infinicyt™ 9 1.8 software. Patient samples, evaluated at diagnosis or during MRD, were individually analyzed for the presence or absence of antigenic expression of each marker used in flow cytometry. CD105, at diagnosis, was expressed in 73.33% of VIII patients with BCP-ALL, with the highest expression in leukemic blasts. When compared with MRD, the highest expression was in hematogonia in negative MRD (67.28%), with a mean MFI of 87.26. When analyzed individually (patient 1), the blasts had a higher expression and MFI, 21.56 and 26.14, respectively. CD105 can be considered a potential prognostic marker for the detection of response to induction therapy in childhood BCP-ALL, and may serve to optimize treatment decisions.

Imiquimod (IMIQ) is a TLR7 agonist that potentiates the antitumor response quickly and persistently, and BCG is an attenuated vaccine (strain) of Mycobacterium bovis, which induces a increase in the activation of the immune system, which can be an essential aid in the antitumor response.

This research aimed to test the effects of IMIQ on experimental melanoma to determine if it is essential to restrict tumor growth and to prolong animal survival after treatment in C57Bl/6 wild-type (WT) and C57Bl/6 CD1-knockout mice (CD1-/-). This study also aimed to test the BCG vaccine as an adjuvant anti- melanoma therapy in wild C57Bl/6 animals. Mice were treated with IMIQ or BCG after injection of tumor cells subcutaneously (s.c) into the pinna of the ear. Parameters for both treatments were evaluated, such as tumor size, survival, and splenic cell phenotypes were analyzed. Furthermore, intracellular cytokines were evaluated after stimulation with anti-CD3. Treatment with IMIQ effectively restricted initial tumor growth and increased survival only in WT animals. Antigen-presenting cell (APC) frequencies were higher in WT animals than in CD1-/- animals, regardless of IMIQ treatment. There was an increase in the number of splenic perforin+ NK+ cells in WT mice and an increase in splenic IFN-γ-producing CD4+ T cells stimulated with anti-CD3 when compared to WT mice with CD1-/- treated with IMIQ. In addition, there was also an increase in splenic CD8+ T cells producing TNF+ in unstimulated splenic cells from WT animals compared to CD1-/- animals. In animals treated with BCG injection in situ, there was reduced tumor growth and increased survival compared to animals that only received tumor cells. There was an increase in dendritic cells and a decrease in splenic Treg cells at the splenic level. Cytokine production revealed a decrease in IL-10, an increase in INF-γ by splenic CD4+ and CD8+ T cells, an increase in INF-γ and perforin and granzyme B factors by NK cells, and an increase in INF-γ by NKT cells. Also, at the tumor level, the histopathological analysis indicated that the animals treated with BCG had a greater cellular infiltrate and a lower percentage of necrosis and muscle tumor invasion. In conclusion, animals treated with IMIQ: WT mice were protected by IMIQ from early mortality, with a decrease in melanoma development. Besides, BCG treatment limited tumor development and significantly increased survival in C57Bl/6 mice, which parallels with strong activation of the immune system, characterized by innate and adaptative responses, and had a more significant infiltration of inflammatory cells and less necrosis, and muscular tumor infiltration.

Considered a disease associated with aging, Chronic Obstructive Pulmonary Disease (COPD) presents airflow limitation associated with chronic lung inflammation involving changes in the respiratory and systemic systems. Risk factors such as smoking, inhalation of harmful gases, and genetic mutations can influence the development of the disease. COPD results from the complex interaction between genetic and environmental factors over time. Both COPD and the aging process share similar mechanisms of immunosenescence. These changes are thought to result in an "accelerated aging" process in COPD patients. The immunosenescence found in COPD is related to the clinical course of the disease, associated with worsening gas exchange, pulmonary hyperinflation, and increased risk of mortality. Pulmonary function testing is a valuable tool in identifying patients at risk of developing COPD. A specific subtype of this disease is known as spirometry with impaired preserved relationship (PRISm). The interference of endocrine aging was identified in individuals with COPD by analyzing DHEA-S (dehydroepiandrosterone sulfate) levels and GH (growth hormone). Accelerated lung, immune, and endocrine aging in the disease are often discussed individually in the literature. Studies that assess how relaxing these systems are require renewed attention, given that COPD is not limited to repercussions only at the local level. The objective of this study was to evaluate the clinical, endocrine, and immunological profile in individuals diagnosed with COPD, as well as in individuals with risk factors for the development of the disease, in addition to reviewing the aspect of immunosenescence in COPD. This study presents a systematic review addressing immunosenescence changes in COPD and discussing their clinical repercussions. In addition, an original article presents the immunoendocrine profile of individuals with COPD and PRISm, as well as the influence of these hormones on lung function and immunological markers.

"Asthma is one of the most common noncommunicable diseases in the world, affecting from 1 to 29% of the population in different countries. The inflammatory process of asthma is associated with immune system activation, airway hyperresponsiveness, epithelial cell activation, mucus overproduction, and airway remodeling. It is well recognized that Th2 cells are the main drivers of eosinophilic allergic airway inflammation, generating abundant amounts of IL-4, IL-5, IL-9 and IL-13. However, asthma in adults is more often non-allergic than allergic. Although inflammation appears as a key feature of the exacerbated response in asthma, anti-inflammatory therapy only reduces this exaggerated response but is not able to suppress it, leading to the hypothesis that other factors besides the inflammatory process contribute to the symptoms. observed in asthma. Barrier tissues, such as the lungs, are innervated by the peripheral nervous system, which detects stimuli, including harmful ones, and responds to them by regulating autonomic reactions. The nervous system in the tract plays an important role in regulating mucus intensity, vascular permeability, airway smooth muscle tone, and blood flow. BDNF is an NT present in the lower airways and may contribute to changes in airway structure and function. In this context, this research aimed to evaluate the impact of variants in the BDNF gene on asthma phenotypes. The association study of the variants was carried out with the population of asthmatic adults from the ProAR. The results showed that the G allele of rs962369 was negatively associated with mild asthma (OR 0.74, 95% CI 0.564-0.985, p= 0.038). The A, G, G, G, T and A alleles of rs6265, rs11030104, rs7103411, rs988748, rs10767664, rs2030323, respectively, were positively associated with a lack of reversibility. The G allele of SNVs rs7124442 was significantly associated with lower chances for atopy (OR 0.75, 95% CI 0.575-0.989, p= 0.041). While the G and A alleles of the SNVs rs2030324 and rs7934165, respectively, were associated with a higher chance of atopy (OR 1.26, 95% CI 1.048-1.516, p= 0.014) and (OR 1.25, 95% CI 1.041-1.506, p= 0.016). G allele of the rs7124442 and A allele of the rs11030119, were associated with an increased chance of exacerbation (OR = 1.575, Pperm =0.037 and OR = 1.823, Pperm = 0.029). Furthermore, the G allele of the SNVs rs7124442 reduced IL-5 and IgE levels and increased blood neutrophil counts. These data show that BDNF gene variants have an impact on asthma in our population.

Asthma is a chronic inflammatory disease of the airways, non-transmissible, influenced by environmental and genetic factors. Allergic asthma is the most common phenotype of the disease and is associated with an exacerbation of the Th2 immune response. Several cell types are involved in the regulation of the immune system in the lung, with emphasis on regulatory cells (Treg and Breg). Several inhibitory controls included by these cells have already been admitted, among which are the release of suppressive cytokines such as IL-10, TGF-β and IL-35. IL-35 is a heterodimeric cytokine, composed of the EBI3 and IL12p35 subunits, which are encoded by the EBI3 and IL12A genes, respectively. Changes in the levels of this cytokine have been associated with asthma and atopy. The consternation of the genetic component in the development of asthma is widely reported in the literature. In this context, given the importance of Treg cells and genetic susceptibility, this study set out to investigate the functional impact of polymorphisms in the regulatory genes EBI3 and IL12A in a population of Brazilian children. DNA from 1.218 children was genotyped using the Illumina 2.5 Human Chip Omni Bead. Logistic regression analyzes were performed using PLINK 1.9 software to verify the association between polymorphisms in EBI3 and IL12A, asthma and atopic markers, adjusted for sex, age, helminth survivors and ancestry markers. mRNA expression was performed using real-time qPCR. A total of 4 markers for IL12A and 5 for EBI3 were found. The surprising results that the C allele of rs2243131 in IL12A was positively associated with asthma (OR 1.35, CI 1.06–1.71), asthma severity (OR 1.36, CI 1.02–1.81), positive skin test for Blatella germanica (OR 1.59, CI 1.09–2.22), and also positively associated with the spontaneous production of IL-5 (OR: 1.71; CI: 1.11–2.62). The A allele of rs568408 in IL12A was also positively associated with a positive skin test for B. germanica (OR 1.65, CI 1.10-2, 37). rs582537 in IL12A was associated with a positive skin test for B. germanica (OR 0.64, CI 0.42-0.98) and Dermatophaoides pteronyssinus (OR 0.77, CI 0.60-0.98), in addition to being associated with the natural production of INF-y (OR : 0.52; CI: 0.52–0.99). With regard to EBI3, all the variants found were incorporated into atopy markers: the C allele of rs78749916 (OR 0.61, CI 0.40-0.93), the G allele of rs77145509 (OR 0.66, CI 0.46-0.94), and the A allele of rs76353132 (OR 0.68, CI 0.43-0.96), were associated with a positive skin test for Periplaneta americana. The rs76353132 variant was also associated with spontaneous INF-y production (OR: 0.72; CI: 0.52-0.99). The rs428253 C allele was associated with a positive skin test for at least one allergen (OR: 0.64; CI: 0.44–0.92), and the rs4905 G allele was associated with a positive IgE for at least one allergen (OR 0.62, CI 0 .40-0.95). IL12A mRNA expression levels were reduced in atopic asthmatic subjects when compared to controls. EBI3 expression levels were decreased in atopic asthmatic subjects compared to non-asthmatic and atopic subjects, and when compared to controls. In this study, we were able, for the first time, to describe new variants in the IL-35 regulatory pathway linked to asthma and atopy, highlighting the importance of immune regulation in the pathogenesis of asthma.

Asthma is a highly complex immune-mediated disease, characterized by a reversible and intermittent obstruction of the airways that, despite having a higher prevalence in childhood, has shown a high incidence and mortality in adults. In recent years, several genomic wide association studies (GWAS) have identified a significant number of genetic variants responsible for asthma susceptibility. These variants have been shown to play an important role in the regulation of gene expression and in the heritability of asthma, including variants in DAD1 e OXA1L genes. The DAD1 gene is known for its role in the regulation of programmed cell death, and OXA1L is described for its involvement in mitochondrial biogenesis and oxidative phosphorylation. The present study aimed to identify new variants in the DAD1 and OXA1L genes and to evaluate the association with asthma and atopy markers in adults. The study involved the participation of 1,084 adult individuals divided into mild to moderate asthma, severe asthma and healthy controls belonging to a case-control study cohort of the Programa
para Controle da Asma na Bahia-ProAR. Analyzes of associations between variants in the studied genes and asthma or atopy were performed using a multivariate logistic regression model adjusted for sex, age, body mass index (BMI), smoking, forced expiratory volume in 1 second (FEV1) and ancestry (PC1) using PLINK 1.9 software. Additive, dominant and recessive genetic models were used for all analyzed variables. In this study, new variants in the DAD1 and OXA1L genes that had never been described before were identified. These genes have been associated with asthma and atopy markers such as skin prick test (SPT), specific IgE for  aeroallergens, eosinophils and Th2-type cytokine production. In silico gene expression analyzes demonstrated that some of the polymorphisms in both genes are able to affect their respective levels of gene expression. Thus, our findings demonstrate that variants in the DAD1 and OXA1L genes may influence asthma and atopy in Brazilian adults. 

In recent decades, the use of biological medications (immunobiologicals) such as anti-TNF agents has gained prominence for the treatment of autoimmune diseases, especially rheumatological ones, such as Rheumatoid Arthritis (RA). The presence of tumor necrosis factor (TNF) as a crucial immune defense molecule in the pathogenesis of autoimmune diseases has made anti-TNF therapy a major step forward in the treatment of chronic inflammatory disorders, but a significant portion of patients do not respond or lose their response to these medications, requiring higher doses or therapy replacement, which have sometimes been associated with variations in genetic factors. There are still no studies that evaluate the response to these medications by correlating them with genetic polymorphisms in the Brazilian population. Therefore, this study aimed to evaluate the association of genetic variants in the TNF pathway with the diagnosis of RA and the response profile to anti-TNF immunobiologics in patients followed in public infusion centers in the state of Bahia, Brazil. In this ambispective cohort study, we used clinical, sociodemographic and genetic data to evaluate the associations of variants in the TNF, TNFRSF1A and TNFRSF1B genes with the diagnosis of RA, standardized scores, laboratory tests and response to treatment with TNFi. 360 healthy controls and 294 patients diagnosed with RA were included. In a subsample, measurements of serum levels of cytokines TNF and IL-6 were performed. Our main results suggest that rs767455-C may play a role in the response to anti-TNF treatment, being related to a better therapeutic response. Additionally, other SNPs such as rs1061622-G and rs1800629-A also seem to interfere with the anti-TNF response profile. Our binary logistic models were able to significantly predict the response to anti-TNFs from a few variables. The rs1800629-A allele and high Visual Analogue Scale scores were shown to be associated with a worse response. Phenotypes such as male sex, use of synthetic medications and seropositive RA seem to contribute to a better response to TNFi treatment. Our results highlight the importance of evaluating the effect of these polymorphisms within the individual's clinical and sociodemographic context with the aim of developing a useful panel in defining clinical approaches in the therapeutic management of RA.

Caseous lymphadenitis, a worldwide disease that mainly affects goats and sheep in Brazil, has as its etiological agent Corynebacterium pseudotuberculosis, a gram-positive bacterium that has a cell wall with a structure called pili responsible for adhesion and made up of pilin proteins, with the SpaC subunit being great importance in cell adhesion, maintaining initial contact with the host, in addition to grouping epitopes capable of stimulating an immune response against C. pseudotuberculosis, data confirmed in the literature through in silico analyses, highlighting the importance of using this method. Bioinformatics tools that characterize in silico analysis were used in this study with the aim of identifying epitopes of the SpaC protein referring to strains PA01, NCTC 4681 and NCTC 4656 of C. pseudotuberculosis associated with MHCII, MHCII and B cells, for construction of a chimeric protein that provides an effective immunological response. Characteristics such as a low number of transmembrane helices, the presence of cytoplasmic domains called signal peptides, the identification of proteins such as transmembrane, extracytoplasmic, analysis of physicochemical parameters and the identification of amino acids in specific regions of these proteins contributed to the selection of the best epitopes in the construction of a chimeric peptide-based protein that can be used in the development of a synthetic vaccine. The final selection resulted in 12 epitopes associated with MHC I and MHCII used to construct the chimeric protein. According to the analyses, the protein was non-allergenic, with great antigenic potential, exhibiting physicochemical parameters that guarantee the stability of the model and interaction with Toll-like 2 receptors, confirming its immunoprotective potential.

Some orofacial injuries are related to the loss of bone continuity and, consequently, to structural and functional damage that impair quality of life. The production of biological tissues from cell cultures is suggested as an auxiliary strategy for orofacial reconstructive surgeries, but the effectiveness of the technique depends on a support structure that guides the formation of functional tissues according to the receptor bed. In this context, the gene expression signature of osteoblastic cells (SAOS-2) cultured on rigid matrices produced with a three-dimensional printer was investigated. To this end, osteoblasts cultured on polylactic acid polycarbonate (PLA), acrylonitrilebutadiene-styrene (ABS M30i) and Polycarbonate-ISO (PC-ISO) scaffolds were evaluated by Array Real time PCR system to determine the expression of genes related to osteoblastic differentiation, bone mineralization, ossification, growth factors, and transcription factors involved in inflammation and healing. The results obtained showed that the ABS-M30i scaffolds, with emphasis on the genes bmp5, bmp6, col9A2, col11A1, spp1, Ibsp, fgf2, vegfA, smad4, smad9, runx2 / bmpr1A, fgfr1 and Igfr1, the PC-ISO with emphasis on in the genes bmp5, bmp6, col19A1, col11A1, cfs2, Ibsp, fgf2, vegfa, smad1, runx2, bmPr1a and Fgfr and the PLA, highlighting the genes bmp5, bmp6, col19A1, col11A1, cfs2, spp1, minpp1, ibsp, fgf2 , tgfb2, smad1, smad5, smad4, bmpr1 and fgr1, allow the expression of a large number of genes responsible for bone formation in vitro, however, PLA seems to have allowed more exuberant expression in the genes that were highlighted, and PC-ISO allowed a more uniform overall response. Thus, the use of the three biomaterials in tissue engineering becomes promising. 

Physalis angulata is a plant that can be found in tropical and subtropical regions,where it is used in folk medicine for the treatment of numerous diseases. Several studies using different components of P. angulata proved anti-inflammatory, antiparasitic, antioxidant and protective action. Therefore, the present work sought to evaluate the effects of the crude ethanolic extract of P. angulata (EEPA) in cell cultures of the PC12 lineage. EEPA was produced from the stems of P. angulata. The cytotoxicity of different concentrations of EEPA was determined using the MTT assay. To evaluate cell morphology and cell proliferation, Rosenfeld dye was used. ImageJ v.1.53e software was used to count the cells. To verify the immune response, nitric oxide levels were analyzed, determined by measuring nitrite using the Griess method. The results were analyzed by the statistical program GraphPadPrism 7.0 and the data were expressed as mean ± standard deviation of the mean of the evaluated parameters. Treatment with EEPA at concentrations 0.5; 1; 5 μg/mL suggest that there was no cytotoxicity or reduction in the number of PC12 cells. The extract caused morphological changes in cells at all concentrations, the most noticeable being the contraction of the cell body. NO production was reduced at all concentrations, mainly at 0.5μg/mL. The data obtained in our work suggest that EEPA can negatively modulate NO production and change the morphology of PC12 cells.

Corynebacterium pseudotuberculosis is the pathogen that leads to caseous lymphadenitis (CLA), an infectious disease that mainly affects small ruminants, associated with economic losses in herds all over the world, including Brazil. CLA leads to the formation of granulomatous lesions in lymph nodes and internal organs. Herd immunization is one of the most used strategies to control infection and spread, but the vaccine formulations available so far do not provide adequate levels of immune protection. The objective of this work is to evaluate the immunomodulatory potential of C. pseudotuberculosis antigens associated with the bacterin of this pathogen and the adjuvant Montanide. Four recombinant antigens were produced in a heterologous system purified by affinity chromatography. Nine sheep were randomly divided into three groups and immunized with: Group 1 (control) – inactivated T1 strain and Montanide adjuvant (T1M); Group 2 – rSpaC, rSodC, rPLD and T1M; Group 3 – rNanH, rSodC, rPLD and T1M. The animals were followed for 240 days, with the animals being challenged on day 90, performing periodic blood collections. The evaluation of the humoral response was done through ELISA, and the evaluation of the cellular response was done through the quantification of interferon gamma (IFN-y). The rSodC, rNanH and rPLD proteins were able to induce a humoral immune response after the first and second doses of the vaccine and after the challenge, remaining constant until the end of the experiment. However, it was not possible to identify any statistical difference in the cellular immune response between the studied groups, nor did it confer protection against C. pseudotuberculosis. Despite modulating a humoral immune response, the vaccine formulations were not able to provide full protection against sheep, indicating the need for further studies to improve the efficacy of subunit-based vaccines.

Glioblastomas are high grade glial cell brain tumors that have a poor prognosis. They have a great capacity for migration, proliferation and invasion into brain tissue, which reduces the chances of treatment success. New therapeutic targets are studied in order to increase the efficacy of treatments and decrease side effects. Analysis and prospection of plant secondary metabolites are being studied as a possibility in the development of new therapies. Physalis angulata L. is a plant species rich in chemical components and promising for the pharmaceutical industry. It has, among many proven benefits, the antitumor and cytotoxic action promoted by physalins and rutin. The objective of this work was to study the action of Physalis angulata L. ethanolic extract (EEPA) on murine glioblastoma C6 tumor cells. As methodology, cytotoxicity was evaluated by MTT. Nitric oxide was dosed by Griess method. Cell migration was analyzed from migration assay. Cell morphology was evaluated by immunocytochemistry with EGFR immunolabeling and Rosenfeld staining method. Protein expression was evaluated by western blotting method. The ability of tissue restoration was analyzed by cell migration assay. The results were analyzed by Graphpad Prism 8.10 statistical program and the data were expressed as mean ± standard error of the mean of the analyzed parameters. As results, it was noted through the MTT assay that EEPA was cytotoxic above the concentration 5 μg/mL, so the concentrations 0.5 μg/mL, 1 μg/mL and 2.5 μg/mL were chosen for modulation of the following experiments. In the analysis of epidermal growth factor receptor (EGFR) expression by immunocytochemistry, there was a decrease in EGFR expression at concentrations 1 μg/mL and 2.5 μg/mL. In the Rosenfeld test, at concentrations 1 μg/mL and 2.5 μg/mL, we had fewer cells and the presence of smaller and thinner stretches and a smaller cell body when compared to controls. Western blotting demonstrated a lower expression of EGFR at the tested concentrations when compared to the control. The migration assay demonstrated an inhibitory capacity of the compound on cell migration. The results obtained in this study may indicate cytotoxic capacity, reduced expression and migratory capacity of C6 cells when modulated with EEPA.

Glaucoma is a very common condition and its diagnosis is often difficult and late. BDNF is a neuropeptide whose trophic function helps protect retinal ganglion cells. Low levels of BDNF have been associated with glaucoma in several studies. In the search for elucidation of the pathophysiology of glaucoma, in this work, we described the frequency of a genetic variant, val66met (rs6265), in a population of glaucoma patients and associated the presence of this variant with the different phenotypes of the disease. To this end, a total of 200 patients were recruited at the Oftalmodiagnose clinic. Patients are followed up in this clinic by the Clinical Protocol and Therapeutic Guidelines for Glaucoma, in which patients receive regular monitoring of the disease and eye drops for its treatment. The diagnosis of primary open-angle glaucoma is made with intraocular pressure above 21 mmHg, papillary cupping above 0.5, and/or visual field defect. 8 ml of venous blood was obtained from each patient, plasma was separated for BDNF measurement via Luminex and the buffy coat was used to extract genomic DNA. Genotyping was performed through real-time PCR using Taqman technology in QuantStudio 12K equipment. The population had a mean age of .65.43 (10.42) years. 46.8% / 38.1% of patients had advanced / severe disease in OD / OS respectively and 53.2% / 61.9% were classified as having an early / moderate disease. We found a low genotypic frequency (7.8%) of the variant allele (T) in relation to the most common one (C). We found no significant differences between glaucoma severity and allele frequencies. We tested BDNF plasma levels among cases and controls. We have recruited ten disease-free controls so far and their levels have also been measured. Mean values were 17.01 (SD 3.92) pg/ml for cases and 365.46 (SD 111.59) pg/ml for controls. This difference was suggestive of statistical significance (p<0.01), despite the small number of samples already examined. Our study suggests that BDNF may be a biomarker for the diagnosis of glaucoma

Obesity is a complex and inflammatory disease associated with morbidity and
mortality. Systemic inflammation is present in children and adults with obesity, it starts in
visceral adipose tissue (TAV) and seems to be central to the development of insulin resistance
leading to hyperglycemia and later to DM2, in addition, it may be important in the
pathogenesis from other diseases. Objective: To identify variants associated with overweight
in Brazilian children through genome-wide association studies (GWAS) and two candidate gene
studies. Methodology. The GWAS was performed on 1004 children (5-11 years old) from a
cohort in Salvador, Brazil. About 15.6% (157) were overweight. Genotyping was performed
with Illumina 2.5 Human Omni Bead Chip. For the candidate gene studies, logistic regressions
were performed, adjusted for sex, age and ancestry markers for the IL10, IL1RL1, IL1B, IRF4,
TNF, IL6, IL33 and PPAR-γ genes in the PLINK 1.09 software. Results: Overweight, obese and
severely obese children were considered overweight. For the analysis of GWAS, eight most
significant variants were found throughout the genome. The first strongest signal was for
rs57281665 (OR: 1.39) which is located in IL1R1, followed by rs9294705 (OR: 1.54), in the
LOC105377841 region between ADH5P4 and EYS genes; rs9294707 (OR: 1.54), rs11964751
(OR: 1.54), followed by rs941292819 (OR: 1.63) located at ST18; rs941292819 (OR: 1.48)
located in KNTC1; rs368540054 (OR: 1.59) located in RAPTOR; rs74497385 (OR: 1.40) located in
DISCAM. For the study of variants in inflammatory genes, 16 SNVs were associated with
overweight. Ten variants in the IL1RL1 gene, two in the IL1B gene and one in the IRF4
increased the risk of being overweight. In the candidate gene study with PPARγ, twenty-one,
five in the additive model were found to be associated with obesity risk, three had an odds
ratio greater than two rs4135268 (risk allele C), rs13083375 (risk allele G) and rs13064760 (risk
C allele). In the dominant model, eighteen variants were found for obesity risk, three had an
odds ratio greater than three rs2028759 (risk allele G), rs1175542 (risk allele A) and rs709150
(risk allele C) indicating risk three times higher for obesity. In the recessive model, of the three
variants associated with the same outcome, the three also had an odds ratio greater than two
rs4135268 (risk C allele), rs13083375 (risk G allele) and rs13064760 (risk C allele), indicating
twice the risk for overweight. Conclusion: The RAPTOR gene locus was the only one found in
other studies and associated with obesity, including in children. Loci in the IL1R1, ST18, KNTC1
and DSCAM genes were identified as novel genes in plausible biological pathways for
overweight. The region LOC105377841 was hitherto unknown in the pathogenesis of obesity.
Genetic variants in pro-inflammatory genes may modulate the expression of these genes
contributing to overweight. Risk alleles in variants in the PPARγ gene may contribute to
overweight. Replication studies should be conducted in order to confirm the regulatory
potential of these genetic variants and advance the understanding of the development of
pediatric obesity and the real contribution of polymorphisms in obesity.

Neospora caninum is an obligate intracelullar protozoan, belonging to the phylum Apicomplexa, capable of infecting several animals, including ruminants and canids. The infection of nervous system cells by this parasite is well established in the literature and has been the subject of studies because of the peculiarity of the immunological mechanisms induced by the infection. In this way, infection has been used as an infectious model to improve the  understanding of the immune responses produced by cells of the nervous system. In parallel with these studies, magnetic stimulation has therapeutic potential in several human disorders. But studies with this technique have not developed into infectious models. Thus, the objective of this work was to evaluate the use of magnetic stimulation therapy in cultures of rat glia infected by N. caninum. Primary culture of glial cells were obtained from the cerebral cortex of newborn Wistar rats (&lt;48 hours). The cultures were infected with N. caninum and after 6 hours of infection, they were treated with magnetic stimulation at a frequency of 10 Hz, at 0.62T intensity for 30 seconds for 3 days. In parallel, glial cells stimulated by LPS and the control group (glia only) were treated with magnetic stimulation. After 72 hours of infection, the experiment was terminated and analyzes of MTT, production of nitric oxide, GFAP, TNF and IL-10 and mRNA expression for NOS2, CCL2, CCL5, KAT and KMO were performed. The results demonstrate that magnetic stimulation has an anti-inflammatory effect in the LPS-stimulated model and that it improves the ability of glial cells to respond to the infectious process, increasing TNF production and modifying cell morphology, in addition to decreasing mRNA expression to NOS2 and CCL2. The data obtained suggest that magnetic stimulation produces different effects in infectious model and inflammatory stimulus by LPS, which may indicate that the state of cellular activation may interfere with the effect produced by this technique.

Disseminated leishmaniasis (DL) caused by L. braziliensis is an emerging clinical form of cutaneous leishmaniasis, characterized by the presence of 10-1000 papular, acneiform and ulcerated lesions in more than two anatomical sites. CD8+T cells play a crucial role in the inflammatory response and progression of LD. The senescence profile of CD8+CD57+T cells is associated with tissue damage in cutaneous leishmaniasis (CL). DL is more refractory to treatment, and the establishment of a clinical reference capable of distinguishing patients who will possibly have a good therapeutic outcome from the others is necessary. Methods: Individuals with CL and LD were recruited, skin and blood samples were collected, and data for lesion determination were obtained from medical records. Peripheral blood mononuclear cells and biopsies were used for selection and separation of CD8+T cells, differentiation of monocytes into macrophages, culture stimulated with soluble Leishmania antigen and autologous co-cultures with macrophages infected or not with L. braziliensis. The cell profile was determined by flow cytometry, and cytokines were measured in the culture supernatant by ELISA. Statistical analyzes were performed for each experiment using the Mann-Whitney tests, and Kruskal-Wallis post-tested by Dunn's test, and Pearson's Correlation. Conclusions: Apparently, CD8+CD57+ T cells can promote the lysis of infected cells by cytotoxicity, leading to the release of intracellular amastigotes, contributing to the spread of the parasite in
DL.

The enteric nervous system (ENS) is known as the “second brain” and is an important component of the intestinal wall. Activities such as control of intestinal motility, mucosal integrity, digestion, synaptic transmission, neuroprotection and neurogenesis, in addition to participating in the defense of the intestinal barrier, are performed by the ENS. Recent findings have shown that enteric glial cells (EGCs), located in the myenteric and submucosal ganglion of the ENS, play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), a neurodegenerative disorder characterized mainly by the progressive loss of dopaminergic neurons in the substance nigra pars compacta that generates motor and non-motor dysfunctions, including gastrointestinal dysfunction. The ENS is closely related to the gut microbiota and recent studies demonstrate an intimate relationship between the brain-gut axis. This work aimed to investigate the effect of the flavonoid rutin on the enteric system and intestinal microbiota in an experimental model of Parkinson's disease. We used an animal model in which adult male Wistar rats were subjected to stereotaxic injection with 6-hydroxydopamine (6-OHDA) or saline, treated or not with Rutin (10 mg/Kg) for 14 consecutive days. For damage characterization, the animals were submitted to behavioral tests and brain tyrosine hydroxylase immunostaining after euthanasia. Intestinal segments (ileum and colon) were collected, and histological analysis was performed by hematoxylin and eosin (HE) staining and immunohistochemistry for neurons (HUc/d) and enteric glial cells (S100b) in the myenteric plexuses. We performed intestinal contractility test and qPCR on feces to verify the composition of the intestinal microbiota. The results showed that treatment with rutin is able to improve intestinal transit in parkinsonian animals, in addition to demonstrating that treatment with rutin increases ileal muscle reactivity by muscarinic activation, reduces relaxation through the signaling pathway of nitric oxide donors and increases longitudinal contractility of colonic musculature in parkinsonian animals. It was also observed that striatal injection of 6-OHDA affects the intestinal wall of rats and rutin treatment reduces the amount of intraepithelial lymphocytes (IELs). Although there are reports of modification of the intestinal microbiota in parkinsonian patients, we did not observe changes in the families of intestinal bacteria studied in this work. Finally, the results indicate that the flavonoid rutin has modulatory activities on the ENS with a protective effect against inflammatory damage without interfering with the cell population, in addition to increasing ileal smooth muscle reactivity and increasing intestinal contractility in experimental models in parkinsonian animals.

The spread of the Zika virus (ZIKV) in endemic regions of other established flaviviruses, such as Dengue Virus (DENV), has increased the complexity of diagnosing flaviviruses and the demand for new detection tests specific for the pathogens. Flaviviruses have high protein similarity, and consequently, a variety of epitopes in common that allow the occurrence of cross-reactions to antibodies from viral infections to different flaviviruses. In line with the demand for more specific antigens, the present work aimed to produce antigens with greater specificity for ZIKV, in order to support the development of immunodiagnostic assays. Using bioinformatics tools, unique epitopes of ZIKV were identified in predictively antigenic regions of E and NS1 proteins. The ZIKV E protein was highlighted by the region 146-182 (domain I), and led to the proposal of producing a recombinant antigen based on in tandem repeats of the fragment 146-182 (Tan_E). While the computational analyzes suggested a greater identity to ZIKV in the 220-352 fraction of NS1, which led to the proposal of the recombinant production of partial NS1 (pNS1). Despite the computational predictions, we demonstrated that the 146-182 region, in its tandem presentation, was not conformationally reactive in dot blot and ELISA assays, as well as in its denatured form in western blot assays. In turn, the undenatured pNS1 of ZIKV showed greater specificity to IgG+ sera of ZIKV, which highlights it as a possible tool in the diagnosis of ZIKV by dot blot. Overall, the study tried to elucidate questions about the reactivity of specific regions of the E and NS1 proteins of the ZIKV, such as the low reactivity of the 146-182 region of the E protein, contrary to computational projections, and the reactivity of the 220-352 fraction of NS1, which proved to be specific for ZIKV by dot blot, in order to support studies related to the development of new immunodiagnostic methods.

Corynebacterium pseudotuberculosis is one of the etiologic agents causing lymphadenitis or pneumonia in humans, and caseous lymphadenitis in goats and sheep. The current serological diagnosis for animals has a protocol of low specificity and sensitivity, and in humans there is no diagnostic kit of this nature. In this work, we intended to evaluate the antigenic potential of four recombinant proteins of C. pseudotuberculosis (rSodC, rPknG, rNanH and rSpaC) in goat and sheep sera and two of them (rPknG and rSodC) in human serum. In the animal model, goats and sheep were experimentally infected with inoculums of CAP76, CAP21 or VD57 strains (n = 16), and another group of these animals was not infected (n = 12). In the human model, serum was obtained from two groups: Group 1: participants who care for goats and sheep (n = 14), and Group 2: participants who reported not having contact with these animals (n = 25). Recombinant proteins were produced in E. Coli BL21 (DE3) Star, and antigenicity was evaluated using ELISA and/or Western blot techniques. Homology analyzes and epitope prediction of rPknG and rSodC were performed in silico. With the results obtained, it can be suggested that rSodC is a strong
candidate as a tool for the diagnosis of infection by C. pseudotuberculosis in goats and sheep. In the human model, rPknG and rSodC reacted indiscriminately, with no difference between the evaluated groups. It was observed, in the in-silico analyses, that rPknG and rSodC have high homology coverage with other species of the Corynebacterium,
Mycobacterium, Rhodococcus, Nocardia (CMRN) group.

Asthma is a chronic inflammatory disease of the lower airways, characterized by hyperreactivity, mucus production and airway obstruction. Several factors influence its susceptibility and development, including genetic variability. The mTOR gene encodes an evolutionarily conserved serine / threonine kinase that plays a central role in the integration of environmental signals in the form of growth factors, amino acids, in the regulation of several immune cells, including neutrophils, mast cells, natural killer cells, T cells γδ, macrophages, dendritic cells (DCs), T cells and B cells. In search of variants in MTOR due to its central importance in the metabolism of the immune response, the possible interference of single nucleotide variants, SNPs, is admitted in the qaudro asthmatic. The MTOR gene is activated during the onset of asthma and suppressed during asthma remission and inhibition of the mTOR pathway in asthmatics decreases the expression of asthmatic markers and restoring the pattern of Th17 / Treg and Th1 / Th2 cytokines. The objective of this work is to investigate how variants in mTOR are associated with asthma, atopy and therapeutic response. The study was carried out in the PROAR population, where samples from adult individuals were genotyped using the Illumina Infinium Multi-Ethnic AMR / AFR-8 Kit chip. Association analyzes were performed using the Plink software. The variants rs1057079, rs7525957 and rs12122483 were associated with airway asthma. While the rs1057079 and rs7525957 variants were associated with the atopy phenotype. In addition, eight variants were associated with significant eotaxin production, in addition to IL 8 with four variants, IL 12 with three variants, IL 17 and IL 5, both with two. Therefore, these variants in a single nucleotide can assist in better understanding of asthma and its therapeutic strategy and have the potential for future functional studies to better understand this pathway. 

Visceral leishmaniasis (VL) is one of the most important emerging diseases in the world,affecting mainly dogs and humans. One of the most prevalent molecules on the surface of Leishmania infantum is the lipophosphoglycan (LPG), which has high antigenic power, is highly stable and easy to extract. This work aimed to develop an immunochromatographic test for dogs using LPG as antigens, to test the use of LPG in an ELISA for human LV (LVH) and to evaluate the presence of anti-LPG antibodies as a marker of response to the treatment against the disease in dogs. For the standardization of the rapid test (TR-LPG LVC), 20 serum samples from symptomatic dogs, 20 from asymptomatic dogs, and 30 from dogs from a non-endemic area for VL were used; cross-reactivity was tested with sera from dogs naturally infected by Leishmania braziliensis (n = 10) and dogs vaccinated with Leish-Tec® (n = 7). In the ELISA for LVH, were used 45 serum samples from symptomatic patients, 45 samples from patients from a non-endemic area, and serum samples from patients infected with Trypanosoma cruzi (n = 20) and L. braziliensis (n = 20) were used for the cross-reactivity test. In the ELISA LPG for dogs under treatment, serum samples from 7 dogs that responded to the treatment and from 8 that did not respond, at six different times of treatment, were used and the results were compared with the ELISA using a total antigenic lysate as antigen. The TR-LPG LVC gave a sensitivity of 70%, specificity of 96.6%, recognized 81.8% of asymptomatic dogs and did not cross-react with L. braziliensis. The ELISA for LVH conferred a sensitivity of 71.1%, specificity of 64.4% and cross-reacted with the two species tested. The recognition of LPG was not differentiated in dogs that responded or not to the treatment. As a conclusion, although LPG shows to be a promising molecule for use as an antigen in the rapid test, further adjustments in the standardization of the method are still needed to improve sensitivity. In addition, LPG did not prove to be an adequate antigen in the immunodiagnosis of LVH, and recognition of LPG is not a determining factor to differentiate dogs that respond or not to the treatment.

Streptococcus equi subsp. equi and Streptococcus equi subsp. zooepidemicus, cause significant socioeconomic impact in the context of equine culture. S. equi subsp. equi is the agent of equine strangles, a disease of great prevalence among horses, and S. equi subsp. zooepidemicus is an opportunistic bacterium that causes lower tract inflammator disease and can infect other organisms, including humans. In this work, we use in silico approaches to propose immunogens and drugs against diseases associated with these bacteria. For this, we selected 18 complete genome strains from the two S. equi subspecies, predicted the orthologous proteins and the subcellular location of these proteins. We also predicted four proteins associated with virulence located in the cytoplasm and simulated their interaction with natural compounds to select the best ones capable of destabilizing the bacterial cell. Among the proteins located in the outer membrane and secreted by the bacteria, we predict six as potential vaccine candidates. We searched for high-affinity epitopes to molecules of MHC I, MHC II, and B cells that induce an immune response. The selection of the best epitopes led to the construction of a molecularly stable and antigenic chimeric protein with immunogenic potential against the subspecies. We predict its three-dimensional structure, simulate its interaction with TLR2 and predict its ability to be produced in the laboratory for further in vitro tests. In conclusion, we present immunogen and drugs with potential use in combating diseases caused by both subspecies in horses and these results can direct the efforts of in vitro and in vivo experimentation for the development of new biotechnological products. 

There is no evidence evaluating the IL10 gene epigenetic up regulation among mestizo children in a high-altitude city in Latin America. Objective: to identify polymorphisms and methylation profiles in the IL10 gene associated with asthma in children aged 5 to 11 years in the urban area of Cuenca. Methods: a case-control study was carried out with asthmatic and non-asthmatic children aged 5 to 11 years in Cuenca. Data on allergic diseases and risk factors were collected through a questionnaire applied to parents. Atopy was measured by skin test reactivity (SPT) using a panel of relevant aeroallergens. Three IL10 single nucleotide polymorphisms were evaluated in all participants and methylation analyzes were performed in 54 study participants. Associations between risk factors, allergic diseases and genetic factors were estimated using multivariate logistic regression. Results: the results of polymorphisms showed that there are no differences between cases and controls when comparing the allelic and genotypic frequencies of SNPs rs3024495, rs3024496, rs1800896. In the methylation analysis, no differences in methylation in the promoter region of the IL10 gene were found between cases and controls, however, the multivariate analysis showed an association of the mother&#39;s smoking habits with the methylation of the promoter region of the gene, which indicates the importance of environmental exposure in the modulation of gene expression.

Sickle cell disease (SCD) is caused by a mutation of β-globin, which leads to recurrent vessel occlusion and ischemia resulting from the loss of hemoglobin conformation which leads to deformation of the red blood cell. In Brazil, the prevalence of the βS allele can be on average 10.9%, depending on the region. Systemic inflammation is one of the characteristics derived from recurrent vaso-occlusion and ischemia in DF. Some authors suggest that 50% of adults with homozygosis of hemoglobin S (Hb SS) will develop osteonecrosis of the femoral head secondary to DF at around 35 years of age. Recent studies have demonstrated the important relationship between a greater chronic inflammatory state and more severe clinical symptoms, suggesting a crucial role of the immune system in Pathophysiology of DF. Recent evidence suggests that abnormalities involving CD4 + T lymphocytes (TCD4 +) are associated with the pathophysiology of osteonecrosis (ON), however, few studies address TCD4 +cells in ON secondary to sickle cell disease (SCD / ON). In addition, T cells that produce several cytokines simultaneously are often present in the inflammatory medium and may be involved in the immune response seen in DF / ON. In the first part of this study we characterized the functional status of TCD4 + cells in SCD by simultaneously determining the frequency of IFN-γ +, IL-4 + and IL-17 + TCD4 + in cell cultures under exogenous stimuli. In the first part of this work, we used peripheral blood mononuclear cells (PBMC) from 9 patients with steady-state DF, 15 patients with DF / ON and 19 healthy controls to quantify the functional status of CD4 + T cells. Bone marrow mononuclear cells (BMMC) of 24 patients with DF / ON (SCD BM) and 18 patients with ON not related to DF (non SCD BM) were also analyzed. We have shown that PBMC of people with SCD who do or do not have ON had significantly reduced frequencies of TCD4 +, TCD8 + and TCD4 + cells, and an increased frequency of circulating CD4 + T cells capable of simultaneously producing IFN-γ + / IL4 + and IL- 17 + / IL4 + compared to healthy controls. Faced with polyclonal stimulation, we saw an increase in t he frequency of TCD4 + cells that Sickle cell disease (SCD) is caused by a mutation of β-globin, which leads to recurrent vessel occlusion and ischemia resulting from the loss of hemoglobin conformation which leads to deformation of the red blood cell. In Brazil, the prevalence of the βS allele can be on average 10.9%, depending on the region. Systemic inflammation is one of the characteristics derived from recurrent vaso-occlusion and ischemia in DF. Some authors suggest that 50% of adults with homozygosis of hemoglobin S (Hb SS) will develop osteonecrosis of the femoral head secondary to DF at around 35 years of age. Recent studies have demonstrated the important relationship between a greater chronic inflammatory state and more severe clinical symptoms, suggesting a crucial role of the immune system in Pathophysiology of DF. Recent evidence suggests that abnormalities involving CD4 + T lymphocytes (TCD4 +) are associated with the pathophysiology of osteonecrosis (ON), however, few studies address TCD4 + cells in ON secondary to sickle cell disease (SCD / ON). In addition, T cells that produce several cytokines simultaneously are often present in the inflammatory medium and may be involved in  the immune response seen in DF / ON. In the first part of this study we characterized the functional status of TCD4 + cells in SCD by simultaneously determining the frequency of IFN-γ +, IL-4 + and IL-17 + TCD4 + in cell cultures under exogenous stimuli. In the first part of this work, we used peripheral blood mononuclear cells (PBMC) from 9 patients with steady-state DF, 15 patients with DF / ON and 19 healthy controls to quantify the functional status of CD4 + T cells. Bone marrow mononuclear cells (BMMC) of 24 patients with DF / ON (SCD BM) and 18 patients with ON not related to DF (non SCD BM) were also analyzed. We have shown that PBMC of people with SCD who do or do not have ON had significantly reduced frequencies of TCD4 +, TCD8 + and TCD4 + cells, and an increased frequency of circulating CD4 + T cells capable of simultaneously producing IFN-γ + / IL4 + and IL- 17 + / IL4 + compared to healthy controls. Faced with polyclonal stimulation, we saw an increase in the frequency of TCD4 + cells that produced IFN-γ + and T CD4 + producing IL-17 + in BMMC from SCD BM compared to non-SCD BM. The increase in the proportion of CD4 + T cells capable of producing a broad spectrum of pro-inflammatory cytokines after a strong stimulus indicates that the immune system in patients with SCD / ON has an expressive pool of partially differentiated cells ready to assume an effective function. Possibly, this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and pathophysiology. The findings described led us to the second part of this study, which was to investigate whether the MSCs of people with SCD / ON had the ability to inhibit the proliferation of TCD4 + cells. Based on the findings seen in TCD4 + cells and knowing the immunomodulatory capacity of MSCs, we seek to evaluate the immunomodulatory potential of bone marrow-derived MSCs in the proliferation of TCD4 + cells derived from peripheral blood mononuclear cells, and factors secreted, in vitro, from volunteers with DF / ON and without DF and ON. we found a strong inhibition of the proliferation of TCD4 + cells when co-cultured with MSCs from individuals with SCD. We identified differences in the cytokines of the co-culture supernatant with control PBMC and DF / ON, where DF / ON showed an increase in the secretion of IL-2, and IL-10, while there is a reduction in the cytokines IFN-γ, IL-4 and IL-17A, which shows a reduction in the metabolism of Th1, Th2 and Th17 cells with an increase in the regulatory cytokine IL-10. Produced IFN-γ + and T CD4 + producing IL-17 + in BMMC from SCD BM compared to non-SCD BM. The increase in the proportion of CD4 + T cells capable of producing a broad spectrum of pro-inflammatory cytokines after a strong stimulus indicates that the immune system in patients with SCD / ON has an expressive pool of partially differentiated cells ready to assume an effective function. Possibly, this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and pathophysiology. The findings described led us to the second part of this study, which was to investigate whether the MSCs of people with SCD / ON had the ability to inhibit the proliferation of TCD4 + cells. Based on the findings seen in TCD4 + cells and knowing the immunomodulatory capacity of MSCs, we seek to evaluate the immunomodulatory potential of bone marrow-derived MSCs in the proliferation of TCD4 + cells derived from peripheral blood mononuclear cells, and factors secreted, in vitro, from volunteers with DF / ON and without DF and ON. we found a strong inhibition of the proliferation of TCD4 + cells when co-cultured with MSCs from individuals with SCD. We identified differences in the cytokines of the co-culture supernatant with control PBMC and DF / ON, where DF / ON showed an increase in the secretion of IL-2, and IL-10, while there is a reduction in the cytokines IFN-γ, IL-4 and IL-17A, which shows a reduction in the metabolism of Th1, Th2 and Th17 cells with an increase in the regulatory cytokine IL-10.

Asthma is one of the most common chronic inflammatory diseases, especially in children. The prevalence of childhood asthma differs widely in Latin America and is correlated with genetic and socio-environmental factors, with a considerable increase among populations with multiple ethnicities, especially among those with greater African ancestry. Admixture mapping has been shown to be a useful tool in revealing new loci associated with asthma and lung function in mixed populations, however, such studies are focused on North American populations, and the influence of local chromosomal ancestry on the development of asthma in Latino populations is not entirely understood, particularly in Brazil. The present study aimed to identify genetic loci that contribute to asthma susceptibility and variations in lung function measurements in Latin Americans. The investigated population included 1,214 unrelated children aged 4 to 11 years from low- and middle-income communities in the city of Salvador, Northeastern Brazil, members of the Social Changes Asthma and Allergy in Latin America (SCAALA) cohort - Salvador. The population of Salvador is predominantly black and brown and marked by high socioeconomic inequality. The thesis was structured in two chapters conducted in the population belonging to SCAALA - Salvador, the Admixture Mapping was carried out for both, the first being developed based on lung function measurements and the second based on the clinical phenotype, asthma symptoms. In the first article we evaluated the association between local chromosomal ancestry and measures of lung function, it was identified that African ancestry in regions 17q21.31, 10q22.2 and 2p23.1 was associated with lower measures of lung function. In contrast, European ancestry at 17q21.31 had an opposite effect. In addition, five genetic variants were replicated in the adult cohort in the city of Pelotas “1982 Pelotas birth cohort”. In the second article, local ancestry was associated with asthma symptoms. Two new loci at 13q12 and 4p12-4p13 were identified, in which African ancestry at 13q12 and 4p12-4p13 was negatively associated with asthma symptoms, whereas European ancestry at locus 4p12-4p13 was associated with risk for asthma. A to tal of seven variants were associated with the addressed phenotype. Furthermore, the variants were correlated with the concentration of IFN-γ and IL-13 cytokines, lymphocyte production and atopy markers. These findings suggest that genomic regions associated with ancestry may contribute to the genetic architecture of lung function measurements and may help to explain the pattern of genetic risk for asthma in African- American children in Brazil.

Co-infection by the Acquired Immunodeficiency Virus (HIV) and the Human T-cell Lymphotropic Virus (HTLV) represents a worldwide health problem. A study showed that Salvador-Ba had a prevalence of 16.3% of HIV-1/HTLV-1 coinfection. Coinfected individuals have a higher risk of developing pathologies associated with
both viruses, making it necessary to understand how T lymphocytes and monocytes behave during HIV-1/HTLV-1 coinfection, aiming to clarify the immune mechanism and its effects so that these cells can be used as therapeutic strategies for treating the pathologies associated with both viruses. Therefore, the profiles of T lymphocyte and monocyte expression in the influence of HIV-1/HTLV-1 coinfection were evaluated. The study included 15 HIV-1 monoinfected individuals, 14 HTLV-1 monoinfected individuals, 15 HIV-1/HTLV-1 coinfected individuals and 20 healthy individuals. The expression of T lymphocytes and monocytes were obtained by flow cytometry and statistically analyzed. According to the findings of the first study, we can suggest that co-infection may favor the progression of pathologies, especially those associated with HTLV-1. A decrease in the expression of naive CD4+ T cells was observed among co- infected individuals. The expression of TCD4+ lymphocytes was also reduced in co- infected individuals compared to those monoinfected by both viruses, which may be related to the dispute of the immune system in containing the virus. It was also demonstrated a decrease in activated CD4+ T lymphocytes in individuals who presented clinical manifestations such as HAM/TSP (HTLV-1-Associated Tropical Myelopathy/Paraparesis), which may suggest an increase in viral activation in these individuals. Our data also suggest that the use of antiretroviral therapy (ART) may favor the increase of some T lymphocyte subpopulations. Regarding the findings of the second study, there are differences between the subpopulations of circulating monocytes among HIV-1/HTLV-1 coinfected individuals in relation to individuals monoinfected by HIV-1 and HTLV-1. Our study demonstrated a lower expression of classical monocytes in HIV-1 monoinfected individuals compared to HTLV-1 monoinfected individuals, as well as in individuals who had clinical manifestations, especially those associated with HTLV-1, which may be a result of use of antiretroviral therapy (ART), since this subpopulation of monocytes responds to different types of ART, and also because these monocytes are more abundant in healthy individuals. On the other hand, the increased expression of non-classical monocytes observed in co-infected individuals compared to HIV-1 monoinfected individuals may suggest the influence of the HTLV-1 virus, as they stimulate the proliferation of this subpopulation of monocytes. 

Zinc (Zn 2+ ) is a trace element involved in numerous biological functions due to its capacity to bind to large number of enzymes. Has an antioxidant effect and is essential for the development of the immune system. In broilers, the immune response can be influenced by nutritional levels or dietary ingredients. The aim of this study was to evaluate the effect of the zinc supplemented diet on the cellular and humoral responses and on the mitochondrial metabolism of these birds. Eight hundred and thirty-two one-day-old 1-day-old male Cobb 500 broiler chickens were used in a randomized design with 4 treatments containing different sources and levels of zinc, (1-Control (basal diet without zinc supplementation); 2- ZnO-100 (diet basal diet+ 100mg of ZnO/of kg feed); 3-Gl-Zn-25 (basal diet + 25mg of zinc glycinate/of kg feed) and 4- Gl-Zn-100 (basal diet+100mg of zinc glycinate/of kg feed) in 8 replicates with 26 birds per pen. A culture of peripheral blood mononuclear cells was performed at 12 days of age to verify the production of nitric oxide and MTT test. A 10% suspension of SRBC was used for evaluation of humoral immune response in 32 birds (8 birds/treatment) which were inoculated with 0.25 mL of 10% SRBC suspension in the brachial vein on days 7 and 21. Blood samples were collected on day 7 after the last inoculation. Subsequently, serum microhemagglutination activity and titers of serum were estimated and antibodies were evaluated. Cell-mediated immunity was assessed by measuring the activity of cutaneous basophils (CBH) to phytohemagglutinin-P at 28 days of age. The population of leukocytes in blood smears and the ratio of heterophils/lymphocytes were also evaluated. In addition, evaluation of the weight of lymphoid organs, histomorphometric analysis of intestinal segments, evaluation of oxygen consumption of isolated mitochondria from the liver and performance characteristics such as feed intake, weight gain and feed conversion were performed. A higher production of nitric oxide, at 6.77 pg/μg of protein, was observed with the level of inorganic zinc (ZnO) in the supplementation of 100mg/Kg (p&lt;0.05). In addition to an increase in cell proliferation with the organic source of zinc (25mg/kg) (p&lt;0.05). There was no significant difference in the cutaneous basophil response to phytohemagglutinin-P, nor in the anti-SRBC antibody titers, as well as in the ratio between heterophils and lymphocytes. An increase in the relative weight of the cloacal pouch was observed with the supplementation of the organic form of zinc (p&lt;0.05). There was no significant difference (p&lt;0.05) in the villi nature of the intestinal segments, nor in the villus/crypt ratio or in the absorption surface. However, there was an increase in the depth of intestinal crypts in the group that received the lowest concentration of organic zinc in the supplementation. It was possible to observe a difference (p&lt;0.05) between the treatment means regarding oxygen consumption, in stages 2 and 4 of respiration with the ZnO-100 treatment compared to the other treatments. Supplementation of the diet with organic zinc resulted in better performance indices compared to the control group, which was reflected in the greater weight gain of the birds during the entire period of the experiment. The results presented suggest that, regardless of the source used, zinc provided better performance indices. In addition, increased cloacal pouch weight and increased cell proliferation suggest that supplementing the broiler diet with zinc may be beneficial to the immune system. 

Atopic asthma is a complex and multifactorial chronic inflammatory disease, determined by environmental and genetic factors, which affects the lower airways with reduced airflow and hyperresponsiveness; increased production of mucus and pro-inflammatory cytokines such as IL-4, IL-5 and IL-13. IL-33, a cytokine of the IL-1 family, released after damage or death to epithelial cells which has the ability to polarize the Th2 response by increasing the release of Th2 cytokines after activating its ST2 receptor in various cells such as lymphoid cells innate cells (ILCs), dendritic cells, mast cells, basophils, eosinophils, T and B lymphocytes, intensifying airway inflammation in asthma. On the other hand, the NLRP3 inflammasome, also present in epithelial cells, when activated results in the release of caspase-1, which acts by inhibiting IL-33 and attenuating the inflammation caused by this cytokine. Genome-wide association studies (GWAS) have sought to better understand which genetic components may be related to asthma and atopy. Genetic variants in the IL33/ST2/NLRP3/CASP1 pathway genes are key to determining specific phenotypes in asthma and atopy and may determine differences in susceptibility or protection to asthma and atopy. In this context, this research aimed to evaluate the impact of polymorphisms in genes in the IL33/ST2/NLRP3/CASP1 route in asthma and atopy. The study of the association of polymorphisms in IL33, IL1RL1, NLRP3 and CASP1 was conducted in two different cohorts. In the SCAALA pediatric cohort, one of our most important results was the association of the rs7925706 variant of the CASP1 gene that had its T allele positively associated with asthma (OR: 1.47, 95% CI 1.11–1.96, p=0.008) and with higher eosinophil levels in asthmatic individuals (p<0.001). In the adult severe asthma cohort of ProAR, the G allele rs4988956 (ST2) had its G allele associated with severe asthma (OR 1.33, 95% CI 1.05-1.70, P=0.021) and SPT for mites (OR 1.34, 95% CI 1.08-1.65, P=0.012). Furthermore, this same allele was associated with higher eotaxin levels in asthmatic subjects (p<0.05). The G allele of the rs10754558 (NLRP3) variant was associated with protection from severe asthma (OR 0.76, 95% CI 0.60–0.96, P=0.025). In addition, individuals with this G allele expressed more NLRP3 (p<0.05) and NLRP3 expression was greater in the group of severe asthmatics (p<0.05). These data show that polymorphisms in IL33/ST2/NLRP3/CASP1 have an impact on the susceptibility or protection of asthma and atopy in our population.

The central nervous system (CNS) consists of several cell types, especially glial cells, important for the function of neurons, highly specialized cells. Glia is represented by astrocytes that contribute to homeostasis in the brain environment and to regulate the immune response beyond the microglia, a cell with immune - effector characteristics in the brain. Neospora caninum is an obligate intracellular protozoan that infects different cell types, having a predilection for encysting in the nervous system where a glia-modulating immune role with activation of tryptophan pathway has recently been observed. This study aimed to characterize the role of this catabolism in primary cultures of glial cells obtained from the brain of N. caninum infected neonatal rats for 24 hours. Infection with this coccidium resulted in morphofunctional changes due to increased GFAP expression and release of inflammatory mediators TNFα, IL-6 IL1β and IL-10 and arginase, observed by qPCR mRNA expression suggesting that glia acts in an attempt to restore system homeostasis, since excessive inflammatory response can cause irreversible CNS damage. The orchestration of cellular functions following infection made it possible to observe increased expression of mRNA for CCL5 and CCL2, molecules that participate in the CNS chemotaxic response. Neospora caninum infection of glia involves tryptophan pathway with shifting to activation of cinnurenine 2,3 monooxygenase (KMO) and increased production of quinolinic acid (QUIN) evaluated by HPLC, suggesting an alternative mechanism to the antiparasitic activity of these cells. On the other hand, glia - neuron co-cultures in medium conditioned by N.caninum glial cell infection also showed activation of tryptophan pathway with increased KMO expression, besides morphological alterations compatible with tissue preservation. These findings confirm that the infection causes gliosis and proves chemotaxic activity of neuroimmune components of nervous tissue, with activation of tryptophan catabolism and quinolinic acid production.

Oral squamous cell carcinoma (OSCC) presents high rates of aggressiveness and metastasis. The oncofetal protein glypican-3 (GPC3) is expressed in diverse malignancies, however little is known about GPC3 in oral cancer. GPC3-positive staining in tumor cell membrane of hepatocellular carcinoma was associated with recruitment of macrophages, immune components with paradoxal roles in tumor microenvironment. In this study, we aimed to investigate in OSCC the expression pattern of miRNAS considered as GPC3 regulators in relation to its tumoral (mRNA levels and protein) expression and M2 macrophages infiltration. The miR-219a-5p, miR-520c-3p, miR-1271a and miR-4510 expression was analyzed in 40 paraffin embedded OSCC. In addition, GPC3 expression (cytoplasm and membrane) as well as CD68+ and CD206+ macrophages infiltration was semiquantitatively evaluated by IHQ. Performing qRT-PCR in 20 fresh OSCC samples, 14 Adjacent Non-Tumor Tissues (NAT) and 05 Distant Normal Tissues, our group previously found deregulated expression of GPC3 in 70% of the evaluated OSCC (upregulated in 20% and downregulated in 50% of cases). The GPC3 mRNA expression levels was significantly decreased in OSCC in comparison to NAT (P = 0.009). Immunostaining in 30 OSCC demonstrated heterogeneous distribution of CD206+ macrophages in intratumoral (IT), periparenchymal (PP) and intraparenchymal (IP) compartments. The CD206+ macrophages were mainly distributed in both IT and PP regions, presenting scarce infiltrating in IP compartment. Our partial results suggests that GPC3 acts in OSCC preferentially as a tumor suppressor gene in late stages of oral carcinogenesis. In addition, corroborate with previous studies that attribute to CD206+ macrophages protumoral functions in peritumoral region.

Acute Leukemia (LA) is a hematological neoplasm characterized by proliferative clonal expansion of hematopoietic cells, with a failure in differentiation that results in excess of immature cells in detriment of functional mature cells, causing bone marrow failure. LA can be classified into two main groups: acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The main objective of this work is to characterize the immunophenotype and epidemiological profile of acute leukemias in the state of Bahia. This is a descriptive, retrospective study of data obtained from a diagnostic reference service. In total, 796 patients were evaluated over 5 years. The study included all individuals who were diagnosed with Lymphoid Leukemia or Myeloid Leukemia. Demographic variables such as age and gender were collected. For a better definition of leukemia, a wide panel of antibodies was used. 57.29% of the cases were diagnosed as AML and 42.71% as ALL. Acute Promyelocytic Leukemia (APL) accounted for 17.5% of AML cases. Comparing non-APL and APL phenotypes, in addition to HLA-DR and CD34, we found significant differences in the CD13, MPO, CD15, CD64, CD2 and CD7 markers. Of the ALL, 277 (81.47%) were of B cell origin and 63 (18.53%) were of T cell origin. Regarding aberrant markers, in non- APL AML, the presence of CD7 is more frequently observed, followed by CD56. In the LLA B, CD66c was followed by CD13 and CD33. This study documented the immunophenotypic profile of 796 cases of acute leukemia in the Bahia’s population. The CD13, MPO, CD15, CD64, CD2 and CD7 markers have a great contribution in differentiating LPA from other AML. CD2 and CD5 are less expressed in the T ALL group that has a leukometry at diagnosis &lt;10,000. Significant differences were found in several antigens evaluated when comparing the group of adults and children. 

Agathisflavone is a biflavonoid formed by two molecules of the flavonoid apigenin. This flavonoid has several biological activities described in the literature, such as antiparasitic, antitumor, hepatoprotective, anti-inflammatory activities and antiviral and neuroprotective activities in different models of study of the central nervous system (CNS). Although it is a privileged system, several neuroinflammatory conditions can affect the CNS, such as infections, neurodegenerative diseases and trauma. Considering the protective effects of agathisflavone and the current context of emergence of viruses that affect the CNS, the first objective of this work was to evaluate the potential of this biflavonoid in modulating neurogenic populations in the Subventricular Zone (SVZ) and modulating the reactive gliosis in vivo. For this purpose, C57 / BL6 hGFAP-EGFP transgenic mice with specific promoter genes to identify astrocytes aged 8 to 11 days (P8-P11) were subjected to two intracerebroventricular injections per day with agathisflavone (100 µM in 2 µL PBS / injection) or PBS + 0.1% DMSO (vehicle) (2 µL / injection) for 3 days. On the 4th day, the animals were sacrificed and brain tissue analyzed by immunohistochemistry to characterize young migratory neurons (DCX) associated with proliferating cells (Ki67) in SVZ, and to characterize reactivity of astrocytes (GFAP) and microglia (Iba-1) in injured and uninjured cortical region. The results showed that in animals treated with agathisflavone there was an increase in the number of hGFAP-EGFP astrocytes in the SVZ domains (dorsal, lateral and horn) without, however, inducing a significant change in the number of proliferating migrating neurons. Additionally, the injection of agathisflavone induced a reduction in the expression of the GFAP protein in the cortical region of the lesion caused by injections of the flavonoid or PBS + DMSO only (control), a marker of astrocytic reactivity. In this region, as well as the non-lesioned site, treatment with agathisflavone also induced a reduction in the number of microglia and with a reactive phenotype. The second objective of the present work was to carry out technological research in order to investigate the pharmacological potential of this and other flavonoids in the face of diseases of viral etiology that can affect the CNS. In order to fulfill this objective, a technological prospecting was carried out using the Pubmed database and investigating the 2011-2020 ‘flavonoid AND antiviral’ operators. Our research resulted in 149 articles with purified flavonoids and extracts of flavonoids with antiviral activities in silico, in vitro and in vivo, with the maximum number of publications being in the year 2019, with different flavonoids with different actions against various viruses, mainly viruses Influenza and Hepatitis C. Also, we have found out in studies developed using in silico, in vitro models or both, that agathisflavone has antiviral activities. The set of results presented in this work on the modulatory effect of reactive gliosis and gliogenesis in the CNS in vivo, confirm the neuroprotective potential of flavonoid agathisflavone and its potential as an adjuvant therapy against CNS diseases, including those of viral etiology

Introduction: vitamin D is a pleiotropic hormone, 90% of which is formed on the skin by the action of UVB rays exposure, and 10% from food. This vitamin is associated with gene regulation of several cells in the body, affecting the function of different systems. In the immune system, vitamin D seems to play an important role in innate immunity and regulatory response, helping to reduce inflammatory processes, configuring a protective factor for autoimmune and allergic diseases. Objective: To investigate the association between vitamin D, atopy and asthma, evaluating genetic parameters of the genes of the vitamin D metabolic pathway. Methodology: This is a cross-sectional study nested in a cohort, which evaluated a total of 942 individuals aged between 11-19 participants of the SCAALA Program (Social Change, Asthma and Allergy in Latin America). For the diagnosis of asthma and asthma severity, the ISAAC phase III questionnaire was used. IgE specific for aeroallergnos (Blomiatropicalis, Dermatophagoydespteronissynus, Blatelagermanicaand Periplanetaamericana) were identified using Immunocap (Phadia). Serum levels of 25 (OH) D were measured by ELISA (IDS). Genotyping was performed using Ilumina'sHumanOmni Biochip. Multivariate logistic regression was performed to investigate associations of interest, genetic analyses were performed on Plink 1.07, as well as on SPSS. Results: Of the studied population, only 38.8% had sufficient levels of 25 (OH) D. Vitamin D deficiency (<20 ng / mL) was associated with a higher risk of atopy in the general population, (OR 1.45; 95% CI 1.05 - 2.00). Vitamin D insufficiency was associated with an increased risk of asthma only in women [(OR 1.74; 95% CI (1.12 - 2.71)]. Vitamin D was negatively correlated with production of IgE specific for D. pteronyssinus (r = -0.11 p = 0.019). The C allele of SNV (Single Nucleotide Variation) rs9279 in VDR, was negatively associated with asthma [(OR = 0.66; 95% CI (0.45-0.97)] and with vitamin D insufficiency [(OR = 0.78; 95% CI (0.70-0.96)]. Two variants in VDR were associated with severe asthma; the A allele of rs2189480 [(OR = 0.34; 95% (CI 0.13-0.89) and the G allele of rs4328262 [(OR = 3.18; 95% CI (1.09-9.28)]. The combination of variants located in the CYP2R1 and CYP24A1 genes (GAC, for rs10500804, rs12794714 and rs3886163, respectively) was negatively associated with vitamin D production [(β =1.24; 95% CI (2.42;0.06)]. When the three varianteswere present, the association  increased[(β = 3.29; 95% CI (-6.19 - -0.39)]. Conclusion: Vitamin D insufficiency is high in adolescents in the city of Salvador. Deficient levels of vitamin D increase the risk of atopy. Sex is a modifying effect of the association of vitamin D with asthma, and this association occurs only in females. Genetic variants in genes in the vitamin D pathway are associated with increased risk of asthma and atopy, and affect vitamin D levels.

Asthma is a chronic inflammatory, complex and multifactorial disease with several phenotypes. Among the severe asthma phenotypes, there is the subtype 'asthma resistant to treatment, where asthma control is not achieved, even using the maximum maintenance treatment. The aim of this study was to investigate immunological and molecular biomarkers of severe asthma phenotypes in a case-control study, in individuals from the ProAr cohort, in Salvador, Bahia, Brazil. 67 subjects were assessed, divided into three asthma subgroups [17 with severe treatment-resistant asthma (SAR), 22 with treatment-controlled severe asthma (SAC) 19 with mild to moderate asthma (MMA)] and a no asthma (NA) control group including 9 subjects. For immunological analysis, cytokines were measured using a multiplex kit using Luminex technology (Merck, Germany) and the differential sputum cell count was performed by cytospin preparations. The total RNA transcriptome (SAR = 2; MMA = 2) was performed on the Ion Torrent S5 platform, using an Ion 540 chip (Thermo Fisher Scientific, CA, USA). The proteome (three samples for the SAR and MMA groups) was carried out by trypsinization and the peptides were analyzed by mass spectrometry coupled to liquid chromatography (LC-MS / MS). The results suggest the presence of a treatment-resistant asthma phenotype characterized by the production of proinflammatory cytokines (IL-6 and TNF), mixed cell profile, independent of the Th2 response. Omic studies have shown positive regulation of inflammatory pathways (TLRs and the JAK-STAT pathways) and under representation of the Hippo pathway and microRNA profile that modulate important inflammatory mechanisms associated with negative regulation of the Hippo pathway.   

In hepatitis C, HCV persistence may cause cirrhosis, liver failure and hepatocellular carcinoma. New biomarkers and the development of efficient screening tests are still necessary to diagnose seronegative anti-HCV IgG patients. Aim: The aim of this study was to investigate the adaptive immune response of anti-HCV IgE antibodies in patients chronically infected with HCV, and to test its use as a biomarker of antiviral treatment. Methods and Results: Twenty patients before and after 12 weeks of antiviral treatment with interferon-α / ribavirin took part of this study. Amplified indirect ELISAs tested IgE antibodies to recombinant antigens from core and from nonstructural proteins NS3, NS4A/B and NS5B with IgG-depleted sera. Immunocytometric assays determined serum levels of cytokines (TNF-α. IFN-γ, IL-4, IL-6 and IL-10). IgE antibodies to the HCV-recombinant antigens were detected in the hepatitis C patients. Except for NS5B IgE antibodies, there was a significant drop in the levels of IgE to Core, NS4A/B and mainly NS3 after 12 weeks of antiviral therapy regardless of the presence of an early sustained virologic response. Conclusions: These results suggest that IgE antibodies to core and non-structural proteins actively participate in the adaptive immune response to HCV infection and that anti-NS3 IgE should be investigated as a biomarker to monitor antiviral therapy and to exclude hepatitis C in anti-HCV IgG seronegative patients.  

The pathogenesis of schistosomiasis is caused by granulomatous inflammation in response to egg antigens, that can results in liver fibrosis of the host. Ultrasound has been used to investigate the morbidity related to schistosomiasis. Evidences have emphasized the role of monocytes in the immunopathogenesis of fibrosis, sice these cells can express cytokines and other markers associated to inflammation and tissue remodeling. The aim of this study was to evaluate the periportal fibrosis in S. mansoni endemic area patients by ultrasound as proposed by WHO and to evaluate the expression of tissue remodeling markers in monocytes from individuals with different degrees of periportal fibrosis. Of the 122 participants examined with ultrasound, 71% had no periportal fibrosis or had incipient fibrosis not excluded, 29% had some level of fibrosis and 3% had advanced periportal fibrosis. Monocytes from 26 individuals were obtained from peripheral blood mononuclear cells and stimulated with soluble egg antigen (SEA). Monocytes were classified in: classical, intermediate and non-classical and evaluated by flow citometry. In general, the expression of MARCO, CCR5, MMP-2 and MMP-9 were higher in monocytes of periportal fibrosis group compared to individuals without fibrosis or with incipient fibrosis not excluded. Expression of MMP-2 and MMP-9 in monocytes of individuals with advanced fibrosis was lower compared individuals with periportal fibrosis. Taken together, these results may indicate that monocytes have a dual role in periportal fibrosis, since they can express markers associated with tissue damage and fibrogenesis, at the same time that they may be important for the catabolism of the extracellular matrix componentes and consequently help to prevent the progression of fibrotic scarring through the liver parenchyma.

The prevalence of allergic diseases has been growing steadily all over the world,
among them asthma is notable for affecting a large part of the world population.
The "hygiene hypothesis" suggests that reducing exposure to infections such as
pathogens, including helminths during childhood, generates an imbalance in the
immune system, resulting in more frequent development of allergic and
autoimmune diseases. Therefore, parasitic infections may act as a protective
factor against these disorders. The use of helminth infections in immunotherapy
is not feasible, but the products of these biologically active parasites may become
a promising alternative, using its immunomodulatory activity. In this study, we
investigated the immunomodulatory effects of the recombinant rTtMIF and
rTtFBPA proteins of Trichuris Trichiura and the rTCys of Toxocara canis, in a
murine model of experimental asthma induced by Blomia tropicalis extract (BtE).
In these experiments, AJ mice were sensitized with 100 μg BtE / animal,
subcutaneous (s.c) and challenged with 10 μg BtE / animal intra-nasal (i.n).
These mice were then treated with rTtMIF, rTtFBPA or rTcCys (25 μg / animal,
s.c) or Dexamethasone (3 mg / kg). Treatment with rTtMIF led to a reduction of
eosinophil peroxidation (EPO) in the lung and the three antigens were able to
decrease EPO in bronchial alveolar lavage fluid (BAL) and serum anti-Bt IgE
levels. Treatment with rTtMIF, rTtFBPA or rTcCys further led to a reduction of
Th2: IL-4 and IL-5 cytokines in the lungs and BAL. No change in IFN-γ production
was observed and there was no significant increase in IL-10 production in the
macerate of the lungs or in the BAL. These results suggest that alternative
treatment with rTtMIF, rTtFBPA or rTcCys may be promising for asthma through
a non-IL-10 dependent mechanism.

Among the complications after allogeneic hematopoietic stem cell transplantation, graft-versus-host disease (GVHD) is the most significant, serious and frequent clinical problem, in addition to be a major cause of post-transplant mortality. The oral cavity stands out because it may be the main or only site of chronic GVHD and may have persistent lesions after resolution in other areas. Tissue damage results in the positive regulation of inflammatory mediators, such as cytokines, chemokines and heat shock proteins (HSP), which play a critical role in the immunopathogenesis of the disease. The present study aimed to analyze the gene expression profile in oral GVHD. For this, the mRNA expression of the cytokines IFN, TNF, IL-1, IL-2; IL-17, IL-17F, IL-21, IL-23A, IL-18, IL-33, IL-10 and TGF 1, the transcription factors RORt, FOXP3, GATA3, NFB1 and NFBIL1, CCL2 and CCL5 chemokines and HSPs 60 (HSPD1), 70 (HSPA4) and 90 (HSP90B1) in peripheral blood mononuclear cells of patients with oral GVHD were quantified. Eight individuals post-transplantation of hematopoietic progenitor cells were selected, of whom 6 had developed chronic oral GVHD (GVHD) and 2 controls that did not have GVHD. Cells were cultured in vitro without antigen stimulation, and the custom real-time PCR array was used to evaluate the mRNA expression of the genes studied. The relative expression of the evaluated genes was up-regulated in the group of patients with oral GVHD, except for IL-12, which was equal between the groups and IL-17A which was down-regulated. The difference in expression of IFN, TNF, IL1, CCL2, HSP60 and HSP90 between the groups is highlighted. These results suggest the participation of inflammatory molecules (cytokines, chemokines and heat shock proteins) in the pathogenesis of oral GVHD. The transcriptomic analysis used herein allowed the observation from the perspective of gene expression signature, with emphasis on the Th1 and Th17 profiles in the oral GVHD.

Atopia e asma vêm aumentando de incidência mundialmente ao longo dos anos. Os fatores envolvidos no desenvolvimento de doenças alérgicas são: mudanças climáticas, infecção por microrganismos e helmintos, contato com alérgenos e predisposição genética. A principal resposta imune aos alérgenos é a resposta Th2 clássica com participação de citocinas   IL-4, IL-5 e IL-13, que culmina com a reação de hipersensibilidade tipo I e a inflamação eosinofílica envolvidas na asma e em doenças atópicas. As células linfóides inatas do tipo 2 (ILC2s) também respondem aos alérgenos liberando as mesmas citocinas produzidas por células Th2 e que recrutam neutrófilos, eosinófilos, produzem IgE e causam degranulação de mastócitos. Variantes genéticas em genes dos receptores CD127, IL17RB e CRTH2 podem alterar a ativação e função das ILC2s influenciando a susceptibilidade para o desenvolvimento da asma e doenças atópicas. Os objetivos deste trabalho foram quantificar a produção de ILC2s entre os endofenótipos de asma e avaliar a influência de polimorfismo nos genes CD127, IL17RB e CRTH2 em atopia e asma em indivíduos acompanhados no Programa de Controle da Asma e Rinite da Bahia (ProAR). Foram quantificadas ILC2s em células mononucleares de sangue periférico de 30 indivíduos (10 asmáticos grave, 10 asmáticos leve e 10 não asmáticos) por meio da técnica da citometria de fluxo. Em adição, foram quantificadas a interleucina TSLP (ligante de CD127) e o receptor solúvel ST2 (ligante de IL-33) em soro desses participantes. Os polimorfismos foram genotipados através de um painel comercial da Illumina. As frequências de ILC2s não foram significativas entre os diferentes grupos estudados. A frequência de ILC2s foi maior em asmáticos grave e atópicos do que em asmáticos grave e não atópicos, além de apresentarem frequência maior de ILC2s em indivíduos asmáticos e atópicos a B. tropicalis. As dosagens séricas de ST2 e TSLP não foram estatisticamente diferentes ente os grupos. Alguns SNPs em CD127 foram associados com asma, gravidade de asma, atopia, obstrução, marcadores de atopia e aumento de neutrófilos no esputo.  SNPs em IL17RB foram associados com asma, gravidade de asma, obstrução e marcadores de atopia, além da diminuição significativa de ILC2s em células do sangue periférico. CRTH2 SNPs foram associados com atopia e marcadores de atopia. Como conclusão, nenhuma associação foi encontrada entre frequências de ILC2 e endofenótipos de asma, sugerindo que o uso de corticóide pode influenciar na ativação de ILC2, assim como na produção de TSLP. Houve um aumento do número de ILC2 em indivíduos atópicos a B. tropicalis. Os SNPs em genes dos receptores de ILC2s demonstraram ser um fator de proteção ou um fator de risco para a susceptibilidade à asma e atopia o que sugere que SNPs em CD127, IL17RB e CRTH2 são importantes determinantes para o desenvolvimento destas condições ou não. Nesta condição, novos estudos são requeridos para um maior entendimento sobre a participação de ILC2s nos mecanismos imunológicos envolvidos em atopia e asma.

The ADAM33 gene is located on chromosome 20p13 and encodes a family member protein A Disintegrin and Metalloprotease (ADAM). This transmembrane protein is mainly expressed in mesenchyma cells, smooth muscle cells and fibroblasts. This gene is involved in extracellular domain shedding, cell adhesion and signaling, as well as in neurogenesis, muscular development, among other biological processes. Studies in several populations have shown that ADAM33 is associated with asthma susceptibility due to bronchial hyperresponsiveness and airway remodeling. In addition, variants in ADAM33 may affect the level of protein expression, thus increasing the risk of severe asthma.This study analyzed the association between single nucleotide variants (SNVs) in the ADAM33 gene with asthma phenotypes, atopy, and investigated the gene-environment interaction (cotinine) in a Brazilian population.Genotyping was performed in DNA samples from 1,308 participants by means of a commercial panel ethnic global Array (MEGA) of 2.0 illuminates (www.illumina.com) in the individuals of ProAr and 1,246 participants of SCAALA using the human Omni bead Chip Kit 2.5-8V1 (Illumina, San Diego, CA).As a statistical strategy, logistic regression analyses were performed using the three genetic models (additive, dominant and recessive) adjusted by gender, age and markers of ascenstrality. The analysis of the regulatory functions and gene expression was performed on in silico platforms. The analyses show that the G allele of the rs573416 SNVs is associated with greater susceptibility to the development of asthma and that the rs183430480 G allele is associated with the protection of asthma severity in the ADAM33 gene in the ProAR case-control study. Tobacco exposure changed the association between rs573416 and asthma, and this association was maintained only in individuals who were not exposed. In SCAALA individuals, variations in the ADAM33 gene have been associated with protection and susceptibility to the development of asthma and atopy. In this way, the variants of the ADAM33 gene play an important role in asthma and atopy in the Brazilian population. New studies are needed to uncover potential functional SNVs, as well as the role of genetic/epigenetic and environmental factors that can lead to symptoms of asthma and atopy.

Bahia is the second Brazilian state with the highest prevalence of human lymphotropic virus type 1 infection and Salvador has about 1.8% of the population seropositive to the virus. This virus is associated with several pathologies, among them adult T-cell leukemia / lymphoma (ATLL), which is aggressive with a high incidence of death and without effective treatment, in which it accounts for 30% of cases of T-cell neoplasms in the country. Thus, the objective of this study is to characterize the epidemiological and immunophenotypic profile of patients diagnosed with ATLL, attended at an oncohematological reference center in Salvador, Bahia, in the period between 2010-2018. The methodology consisted of a descriptive, retrospective of time series study, which cases of ATLL were collected from reports belonging a reference center and of medical reports available from Com-HUPES. These data were treated and analyzed statistically, being observed that the majority of cases were female and that a large part have the most aggressive clinical condition Although the literature reports that ATLL clinical condition are always considered as severe, in this study it was observed that patients can achieve long survival in good clinical conditions, according to the treatment administered. In view of the available results, it is possible to conclude that exist a broad distinction between  the clinical and molecular forms, being may be an important indicator of the evolution of ATLL.

The leprosy reaction is an inflammatory manifestation whose etiologyis associated with changes in the immune system and maybe triggered by concomitantle prosy infectious conditions, such as periodontitis. Periodontitisis a multifactorial inflammatory disease that promotes destruction of tooth support issues and Porphyromonasgingivalis (Pg) as the key pathogen for its establishment. The studyofimmune system molecules, such as immunoglobulins (IgA), may help in understanding the biological plausibility between periodontitis and leprosy reactions. Objective: This research aimed to standardize and evaluate the role of IgA specific humoral immune response against Pg antigens (extract, recombinant HmuY protein and Kgp12 peptide) in the saliva of individuals with and without leprosy reaction. Methods:Two studies related to the theme were performed. In the first one, a standardization was made by the indirect ELISA method (checkerboard) to determine the ideal salivary IgA concentration. The second was a case-control study with 150 subjects. The case group was composed of individuals diagnosed with leprosy reaction, the control group by individuals without leprosy reaction. Pgantigen-specific IgA antibody levels were measured in the participants' saliva by indirect enzyme-linked immunoassay. Results: The coefficients obtained by standardization through the indirect ELISA (checkerboard) signaled a differentiation between individuals with periodontitis based on salivary IgA-mediated response. Regarding IgA production against Pg antigens, statistically significant differences in salivary IgA levels were observed between the groups with leprosy reaction and without reaction, using the bacteria lxtract as antigen (p = 0.04). However, there was no statistical significance with the use of recombinant protein HmuY and peptide Kgp12. When the groups were divided regarding the presence of periodontitis and leprosy reaction, there was no statistically significant difference in salivary IgA levels in relation to Pg antigens. Conclusion: The findings suggest that periodontitis is capable of modulating the specific humoral response to Porphyromonasgingivalis antigens, increasing he salivary IgA levels observed in saliva of individuals with leprosy reaction compared to those without the disease.

COELHO, Raísa Santos. VARIANTS IN LEP, ADIPOQ AND RETN GENES IN ASTHMA PATIENTS - A STUDY OF ASSOCIATION AND MODIFICATION OF EFFECT ACCORDING TO BODY ADIPOSITY. 81f. 2019. Dissertação (Mestrado) Instituto de Ciências da Saúde, Universidade Federal da Bahia.
Asthma and obesity are chronic diseases with increasing prevalence that, besides environmental and genetic factors, have inflammation as a common link. In this sense, cytokines secreted by adipose tissue cells adipocytes and macrophages) with receptors expressed in the lung are pointed to the link between immune regulation involved in the pathogenesis of both diseases. Variations in the genes responsible for the proteins Leptin (LEP), Adiponectin (ADIPOQ) and Resistin (RETN) have been associated with their unbalanced serum levels and consequent metabolic dysfunction that promote impact on asthma and asthma severity. Thus, the aim of this study was to investigate the association between variants of the LEP, ADIPOQ and RETN genes with asthma and how adiposity modifies this association. Different focuses were given to the childhood asthma cohort
study (SCAALA), where atopy was also investigated, and the severe asthma case-control (PROAR), where the association of variants with the severity of the disease was investigated. In both stratifications for adiposity were performed. Anthropometric indices, however, differ between the means (BMI/Age Z-Score for SCAALA, and waist-to-height ratio in the PROAR population). In SCAALA, negative statistics were observed between rs11763517 (allele C) and rs11760956 (allele A) in the additive model (OR 0.76, 95% CI 0.61-0.96; OR 0.75, 95% CI 0, 59-0.96) and dominant (OR 0.75, 95% CI 0.56-0.99; OR 0.70, 95% CI 0.52-0.93), respectively. The G allele of rs6966536 is positively associated, also in the two models: ADD (OR 1.47, 95% CI 1.01-2.15) and DOM (OR 1.49, 95% CI 1.00-2.23). In ADIPOQ, three SNPs were positively associated. G allele of rs822396 in the three models: ADD (OR 1.36, 95% CI 1.08-1.73), DOM (OR 1.35, 95% CI 1.02-1.81) and REC (OR 2 , 04, 95% CI 1.11-3.75), while rs822395 (C allele) non-ADD (OR 1.25, 95% CI 1.03-1.52) and REC (OR 1.63; IC 95 % 1.14-2.32). For comparison, significant association was observed only with overweight in rs6966536 LEP (allele G) (OR 3.16; 95% CI 1.04-9.60) and ADIPOQ, rs3821799 allele C (OR 3.28). 95% CI 1.22-8.77). In PROAR, in individuals without abdominal obesity, rs34124816 (allele C) was negatively associated with the ADD model (OR 0.28; 95% CI 0.11-0.74) and DOM (OR 0.28; 95% CI 0.11-0.74) and rs3745369 (Allele C) positively associated in the REC model (OR 2.88; 95% CI 1.04-7.97). In individuals with abdominal obesity, the C allele of rs10402265 was positively associated in the DOM model (OR 3.73; 95% CI 1.08-12.78). For severe asthma, G allele of rs16861194, in ADIPOQ gene, positive association was observed only in subjects with abdominal obesity (OR 1.50; 95% CI 1.03-2.16). These data demonstrate that variants in the ADIPOQ, LEP and RETN genes impact the observed relationship between asthma and different body adiposity classes. However, functional studies are needed to clarify as hypothesized metabolic pathways for the observed outcomes.

Introduction: Casein lymphadenitis (LC) is a disease that mainly affects goats and
sheep, has as intracellular pathogen Corynebacterium pseudotuberculosis (Cp). The
widespread occurrence and economic importance of this pathogen reinforce the
need to expand studies on its pathogenesis. Cellular immunity is more important than
humoral immunity against Cp and increased pre-scapular lymph node is the most
common clinical sign in CL. This work proposes to evaluate the clinical,
anatomopathological and immune responses of sheep during 190 days of
experimental infection. CEUA-ICS no082 / 2015. Methods and Results: 15 SRD
sheep divided in control group (G1; n = 4) and infected (G2; n = 11). The G2 received
1x107 CFU of Cp strain VD57 and G1 received saline solution. At 13 points,
throughout the experiment, blood was collected for clinical and immunological
monitoring. IgG response by ELISA and in vitro assay of IFN-γ with the Bovigam® kit
and by flow cytometry to Immunophenotyping to evaluate the Average Fluorescence
Intensity (MIF) of functional molecules, surface markers, of some leukocytes as ,
CD4, CD8, CD11b, CD14, CD21 and AB3 Serotec® CD335 in FACS Lysing
Solution-BD®. The data were analyzed using Microsoft® Excel®, Summit-
DakoCytomation® and GraphPad Prism v.6. In the observed results leukocytosis
with neutrophilia was evident in the first days and regularization after fourteenth day
of infection. Six animals of the G2 presented right scalping right lymph nodes and no
animal had visceral granulomas. G2 animals presented seropositivity (ELISA) from
day 7 and a greater release of IFN-γ in vitro in the chronic phase. In the G2 group,
the lowest MIF median value of CD21 (B lymphocytes) was observed in the infection.
In T lymphocytes, there was a lower median value of MIF of CD4 (T lymphocytes) at
the beginning of the acute phase in relation to the control group - G1. In the infected,
the median MIF of CD14 and CD11b in monocytes were higher from time 150.
Conclusion: In the experimental infection with Cp_VD57 a mild infection with absence
of visceral granulomas was observed suggesting the low pathogenicity of this strain.
Differences in cellular and humoral response between the groups of animals showed
that the antigens can be used to assess Cp infection. The protein extract of the
strains used in this study showed antigenic potential in the production of IFN-γ in
animals with chronic LC. The experimental infection by Cp caused a reduction in the
expression of most of the analyzed molecules, mainly in the acute phase.

The first line drug in the treatment of American Tegumentary Leishmaniasis (ATL) is based
on antimonial derivatives. The ATL caused by Leishmania (Viannia) braziliensis has three
distinct forms: localized cutaneous (CL), mucose (ML) and disseminated (DL). CL is the
most common form of presentation, accounting for about 90% of the cases in the endemic
area of Corte de Pedra, Southeast of Bahia. This form presents with ulcerated lesion, with
raised borders, located generally in limbs. However, the rate of therapeutic failure in this
region has been elevated and the long healing period of the ulcerated lesions indicate the need
to use new therapeutic drugs. Recently, we concluded two clinical trials with drugs
administered orally for the treatment of CL. In these trials, Miltefosine proved to be effective
and Fluconazole ineffective in patients infected with L.(V.)braziliensis. We tested the
hypotheses that in fact the intrinsic sensitivity of the parasite determines the therapeutic
response in CL, evaluat in in vitro susceptibility of L. (V.) braziliensis promastigotes and
amastigotes isolated from cases of CL to Fluconazole, Glucantime® and Miltefosine. Drug
sensitivity was evaluated exposing the promastigotes of L. (V.) braziliensis to increasing
concentrations of drugs, followed by assessment of their viability by the MTT method. For
intracellular amastigotes, the activity of the drug was evaluated by the rate of infected
macrophages. In the experiments, the parasites showed a greater sensitivity in vitro to
Miltefosine than to Glucantime and Fluconazol. We conclude that these data corroborate with
the findings of the clinical trials conducted in the study area, indicating that the phenotypes of
response or refractoriness to the treatment of CL are strongly determined by the intrinsic
sensitivity of the parasite to the drugs employed.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the midbrain. The molecular mechanism responsible for the degenerative process in the nigrostriatal dopaminergic system in Parkinson's disease (PD) remains unknown. There are hypotheses that α-synuclein aggregation that generates the formation of neurotoxic protofibrils and dysfunction of the degradation of proteins altered to mitochondrial dysfunction, the generation of oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. Aminochromo is an endogenous neurotoxin that has been suggested as a more physiological preclinical model capable of inducing all five of these mechanisms that are involved in the pathogenesis of PD. Flavonoids have been the subject of numerous studies in relation to their antioxidant, antiapoptotic and anti-inflammatory action. Synthetic Compound JM-20 has also been described as an antioxidant and mitoprotector. This study aims to evaluate the pharmacological effect of 4 compounds, 3 natural (agatisflavone, quercetin and rutin) and one synthetic (JM-20), on neuroprotective potential in Parkinson's disease models associated with α-synuclein. In this study, SH-SY5Y cells were cultured, mouse microglia cells were maintained under optimal conditions and α-synuclein fibrils were generated by shaking for 72 h at 37 ° C. SH-SY5Y cells were maintained with flavonoids and compound JM-20 at concentrations of 0.1-10 μM, and / or 10 μM aminocromo for 24 h. The neuroprotective activity was performed by the calcein AM / propidium iodide test and the analysis of lysosomal dysfunction by lysossensor dye. All flavonoids and JM-20 had a protective effect against aminocrous-induced damage. In addition, all flavonoids did not cause lysosomal dysfunction. Aminochromo induced loss of lysosomal acidity and all flavonoids reestablished the acidification of this organelle. We performed the aggregation inhibition test using 120 μM α-synuclein with agatisflavone and JM20 in proportions of 1: 1 and 1:10 (α-synuclein: Compounds) kept under stirring for 72 h at 37 ° C. Inhibition of α-sin aggregation was performed using OD reading, red congo test and transmission electron microscopy. JM-20 had the ability to interfere in the aggregation of α-synuclein monomers, generating the formation of other species of aggregates and agatisflavone was able to inhibit the formation of aggregates in the 1:10 ratio. Microglial cells were maintained with agathisflavone at a concentration of 0.1 μM for 12, after which agathisflavone (0.1 μM) and / or α-synuclein fibril (2.5 μM) was added for 12 h, agatisflavone was observed to attenuate formation of autophagic vacuoles and microglial activation. We conclude with these results the neuroprotective action of flavonoids and JM-20 and their ability to inhibit α-synuclein associated damage mechanisms and thereby disrupt the progression of neuronal damage occurring in Parkinson's Disease.

Neosporacaninum is an intracellular protozoan capable of infecting a variety of endothermic animals including animals of production. N. caninum is most frequently found in the central nervous system of definitive hosts. Infection by the parasite induces a Th1-type immune response, with the synthesis of pro-inflammatory molecules, which can be polarized to a Th2-like response through regulatory cytokines. The uncontrolled production of pro-inflammatory mediators contributes to progressive tissue damage. Selenium, as well as the plant species Physalisangulata, have biochemical properties of pharmacological importance, especially anti-inflammatory, antioxidant and neuroprotective activities. The present study evaluated the effects of selenium and Physalisangulata (EEPA) treatment on culture of N. caninum infected glial cells. Primary glial cell cultures were obtained from the cerebral cortex of newborn rats (<48 hours) of Wistar lineage. Cells were treated with the different compounds for 24h and then infected with N. caninum for 72h. Cell viability was assessed by dehydrogenase activity using MTT assay. To verify morphological alterations and cell proliferation, immuno-labeling of glial fibrillar acid protein (GFAP), ionized calcium binding-adapter protein 1 (IBA-1) and 5'-bromo-2'deoxyuridine (BrdU) was performed. The immunological response profile was evaluated by tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 4 (IL-4) cytokine levels for the experiments using selenium compounds, and TNF and  nitric oxide(NO)  levels for experiments with EEPA. Selenium concentrations used in the study were not cytotoxic. SeO2 treatment promoted increased cell viability, while N. caninum infected cells showed reduction. The astrocyte and microglial phenotypes of selenium-traded cultures did not differ from the control culture. However, infection led to an increase in reactive morphology and amoeboid microglia even in previously selenium-treated cultures. Cytokine production did not differ between different selenium treatments, except for SeO2 treated and infected cultures that had increased TNF levels. The experiments using the EEPA showed that the extract did not present cytotoxicity at concentrations 0.5 to 150μg/mL. The extract modulated the astrocyte and microglial morphological profile in the infected cultures, and further induced the proliferation of branched microglia. Pretreatment of EEPA infected cultures reduced NO production. The data obtained suggest that SeO2 intensifies inflammation in infected cultures while EEPA modulates the morphology of infected glial cells and NO production.

It is estimated that 1.2 billion of the world's population is infected with Ascaris lumbricoides. The highest prevalence occurs among children living in rural areas of the tropics with limited access to clean water and sanitation and poor living conditions. Ascaris lumbricoides causes a chronic infection of insidious evolution on the health and quality of life of infected people that may impair physical growth, cognitive development, and micronutrient deficiencies. Human genetics has the potential to significantly increase our understanding of parasite-host interactions. In Brazil, especially in Salvador, there are few studies evaluating genetic polymorphisms with helminth infections, and there is no genome wide association study (GWAS) in individuals infected with Ascaris lumbricoides so far. In this way, the present study allowed the description of genetic and epigenetic factors related to resistance/susceptibility to A. lumbricoides infection. According to our GWAS, variants in two genes were associated to the infection, WSB1 (rs7212516). Based in the GWAS data, we evaluated next, using a candidate gene approach, how variants in WSB1 and IL21R are associated to the infection. WSB1 and IL21R variants have been associated with the activation of Th2 immune response. with Ascaris-specific IgE and the production of IL-5 and IL-13 by PBL stimulated by A. lumbricoides antigen. Infected individuals had reduced expression of WSB1 along with an increase of DNA methylation at the promoter region of WSB1. In conclusion, our data show associations between polymorphisms in WSB1 and IL21R genes associated with Ascaris lumbricoides infection and indicate WSB1 and IL21R as potential targets for the modulation for Th2-mediated inflammation. However, further studies should be conducted in order to elucidate the functional impact of such polymorphisms described in this study in Ascaris lumbricoides infection, as well as, replication in other populations.

Strong evidences indicate that helminth infections can modulate allergic and autoimmune diseases through activation of host immunoregulatory mechanisms. In contrast to these evidences, some studies have demonstrated a positive association between parasitic infections and allergic diseases. These contradictions found in the literature can be explained by many factors, among them we can list parasitic infection load, parasite species and host genetic factors. In this context, we have reviewed the Brazilian observations about the relationship between parasitic infections and allergy. After that we check whether host genetic factors linked to helminth infection (Trichuris trichiura) also modulate markers of allergic diseases. For this, two strategies were applied. To identify SNPs associated with T. trichiura infection, we conducted a Genome-Wide Association Study (GWAS). In this study, we found the variant rs1510456, located in an intronic region on chromosome 8, that encodes the SGCZ gene (zeta sarcoglicano gene) was suggestively associated to T. trichiura infection in our population. After this findings, we conducted a candidate gene study with SGCZ and observed other polymorphisms associated with susceptibility to chronic Trichuris infection and protection for allergy markers. Zeta sarcoglycan is an important protein to maintenance of intestinal sarcoplasmic structure and homeostasis. Furthermore, it is from the SGCZ gene that miR-383 is transcripted. This micro RNA has functions such as cell cycle inhibition and anti-inflammatory activity. Thus, we observed that polymorphisms in this gene may be involved in susceptibility to infection and protection for atopy. Individuals with rs7823866 and rs60924482 polymorphisms have both increased susceptibility to T. trichiura infection and protection for atopy. Further studies are needed to elucidate the mechanisms whereby the SGCZ gene may be modulating atopy and susceptibility to infection.

From the sequencing of the genome of Mycobacterium tuberculosis, biomarkers such
as IFN- and IP-10 are being studied for use in disease diagnosis and treatment
monitoring. The objective of this study was to analyze the profile of IP-10 and IFN- in
patients with tuberculosis. Participating in this study were 93 individuals with
sensitive and resistant TB, treated and not treated with anti-TB drugs and 30
individuals without the disease, with negative TCT. Diagnosis of TB was performed
by bacilloscopy, TRM and / or Culture for BK. Flow cytometry was performed for the
analysis of IP-10 and ELISA for IFN-. Statistical analysis was performed with SPSS
version 21. In general, there was no difference between the sexes. The mean age
was 37.9 (± 12.4) years, more than 50% of the individuals considered to be brown or
blacks, with a mean grade of 30.1% (37). The presence of comorbidities (excluding
HIV / AIDS) occurred in 11.4% (14), and the most frequent was diabetes mellitus with
8.1% (10). In the tubes with specific antigenic stimuli of TB, the medians of IP-10 and
IFN- were higher in the groups in disease condition without or with treatment,
compared to the group without TB infection. Both IP-10 and IFN- differentiated
patients and healthy, but, compared to the culture for BK, IFN- was less specific. In
the evaluation of the biological effect the treated groups had a greater ability to
respond to the antigens when compared to the untreated group. It is possible that the
medication used has induced a greater capacity of reaction.

Caseous lymphadenitis (CLA) is a small ruminant disease that is characterized by the development of granulomatose lesions in superficial and internal lymph nodes, as well as in some organs. CLA can be found worldwide causing significant economic losses, its etiological agent is the bacterium Corynebacterium pseudotuberculosis, and there is no commercial available diagnosis tool that presents satisfactory characteristics, as high level of accuracy, low cost and rapid results. The present study had the objective to develop an indirect ELISA for the detection of C. pseudotuberculosis specific immunoglobulins in small ruminants using recombinant proteins. The electrophoretic profiles of the recombinant antigens PLD, CP40, PknG, DtxR e Grx expressed in a heterologous prokaryotic system were analyzed by SDS-PAGE, and the immune recognition of the proteins was analyzed by Dot Blot. The recombinant proteins were employed in a checkerboard system for the standardization of the ELISA conditions. 130 goat’s serum samples and 160 sheep’s serum samples were used for the obtaining of the ELISA validation parameters. Antibodies from a pool of positive serum samples recognized the recombinant proteins, and there was a weak recognition when a pool of negative serum samples was used. The ELISA that was developed for goats using a combination of PLD and CP40 and only PLD for sheep was able to discriminate between positive and negative animals, with 95% sensitivity, 97.5 specificity and 99.3% accuracy for goats and 91% sensitivity, 98.7% specificity and 96.5% accuracy for sheep, respectively. It can be concluded that these developed ELISAs can be used as a high accurate tool in the immunodiagnosis of the infection with C. pseudotuberculosis in small ruminants

HIV / AIDS infection is a problem of great concern to the world's public health. The prevalence of HIV-1 / HTLV-1 and HIV-1 / HCV co-infections varies widely and is influenced mainly by socio-demographic differences, lifestyle, sexual behavior and access to health services. The objective of the study was to characterize the epidemiological profile of HIV-1 patients as well as coinfection with HTLV-1 and HCV virus in the city of Salvador, Bahia, at a reference center specialized in HIV / AIDS, Viral Hepatitis and HTLV. An observational, cross-sectional study was conducted in which data from 905 medical records of patients infected with HIV-1, HTLV-1 and HCV were included between January 2002 and June 2018. From the analyzed charts, prevalence of 76.1% of reactive serologies for HIV-1, 37.5% for HTLV-1, and 3.8% among HCV infections was verified. Co-infections showed 13.6% (HIV-1 / HTLV-1) and 3.6% (HIV-1 / HCV). When comparing the CD4 + lymphocyte counts and HIV-1 viral load between the groups HIV-1 monoinfected and HIV-1 / HTLV-1 coinfected, no significant statistical differences were found between groups. The results of this investigation contributed to an epidemiological update of these coinfections in patients living with HIV / AIDS, aiming to collaborate with the adoption of institutional protocols that will contribute to a better care of this population of patients in the city of Salvador-BA.

Human toxocariasis is a parasitic infection, mainly caused by Toxocara canis and less commonly by T. cati, worms that inhabit the small intestine of dogs and cats, its definitive hosts. During its entrapment stage in tissues, the parasite releases products from its metabolism and from the surface of its cuticle, containing, among others, immunogenic and immunoregulatory molecules. These molecules, as well as those obtained in the larval phase, using the proteomic tool, can be selected and obtained in their recombinant forms, in order to be tested as possible candidates for immunodiagnostic and immunomodulation in inflammatory disorders such as asthma and autoimmune diseases. It is known that parasitic infections can immunomodulate the host, currently some helminthic molecules have been studied as immunotherapeutics for such inflammatory diseases, which actually have limited and ineffective therapeutic arsenal. In addition, the diagnosis of toxocariase, which is determined by the screening of serum IgG antibodies to Toxocara spp by indirect ELISA, using excreted products secreted by T. canis larvae (TES), is a technique that presents low specificity, since it presents cross reactivity with other helminthes. Thus, this work aimed to characterize the proteomic profile of excreted and secreted and larval product of Toxocara canis as well, with the purpose of obtaining molecules with immunomodulatory properties, in order to be tested in the future, in adiction with a potential marker for the diagnosis of toxocariasis. To meet the objectives, this work was divided into two parts: The first one stands out the proteomic findings, in which we identified 646 TES proteins and T. canis larval extract using PAGE 1D-SDS followed by mass spectrometry. We identified a wide range of proteins that may play a role in inducing host immune response, host pathology, and parasite metabolism and survival. Among these proteins, there are potential candidates for new diagnoses and vaccines for use in humans and natural animal host. The second part of this work highlights the characterization of proteins with potencial to be used in the diagnosis of toxocariasis. Through the immunoprotein approach, we selected four molecules (MUC3, TES 26, TES32 and CTL4), which were expressed, purified and tested for their immuno-specific potential for diagnosis. The results indicated that the recombinant molecules responded well to IgG ELISAs and even better to IgG4, with high level of sensitivities and specificities. Immunoblotting revealed absence of cross-reactivity with other species of helminths and environmental allergens. In summary, we identified a range of proteins that may play a role in the induction of immune response in the host and the host pathology, and survival and metabolism of the parasite. . Immunospecificities between the molecules ranged from 92.3% to 97.2% for sensitivity and 88.8% to 98.3% for IgG4. The combination of the rTES 26 molecules with rCTL4 achieved sensitivity and specificity of 100%. These results indicate that the development of a diagnostic test for human toxocariasis with high sensitivity and specificity and stimulate us to progress in the use of these molecules as replacement of TES in indirect ELISA. In addition, we found and tested proteins with confirmed potentials for diagnostic application, which will present good performance in the validation parameters.

Chronic chagasic cardiomyopathy (CCC) is characterized by a myocardium damage associated with intense inflammation and fibrosis. The development of therapies aiming at reducing the progression of CCC is of great importance. Dendritic cells and macrophages are antigen presenting cells (APCs) that can activate the immune response or induce tolerance of T cells, according to their profile and microenvironment. The alternatively activated APCs (aaAPCs) can be induced in vivo and in vitro by dexamethasone and appear as a therapeutic option for the treatment of diseases caused by autoreactive T cells. Here we evaluate the potential of the alternatively activated APC in the development of CCC in an experimental model of Chagas disease. Cell characterization showed aaAPCs expressing CD11b+ and lower expression of PD-L1 and PD-L2. These cells produce low levels of IL-6 and IL-12p70 and higher levels of IL-10 compared to activated APCs. The GFP+ aaAPCs were detected in the inguinal, heart and spleen lymph nodes after 24h and in the heart after 48h of the injection. Morphometric analysis showed reduction of inflammation in the hearts of mice transplanted with aaAPCS, corroborated by a reduction in the expression of CD45 by RT-qPCR. A reduction of fibrosis was also observed. A reduction in the gene expression of pro-inflammatory mediators, IL-6, IL-12, may also be observed. In contrast, a significant increase in the gene expression of the anti-inflammatory cytokine IL-10 and FoxP3 +, and an increase of CD4 + FoxP3 + T cells in mice treated with aaAPCs was observed. In addition, the reduction of the gene expression of molecules associated with fibrosis, such as col1a2 and MMP9, was evidenced. In conclusion, our results show a reduction in CCC due to treatment with alternatively activated APCs because of regulatory T cell-induced immunomodulation associated with increased production of IL-10.