Banca de DEFESA: JUQUELINE ROCHA CRISTAL

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : JUQUELINE ROCHA CRISTAL
DATA : 17/12/2019
HORA: 09:00
LOCAL: Faculdade de Medicina da Bahia
TÍTULO:

PERFIL TRANSCRIPTÔMICO DE LESÕES PROVENIENTES DE PACIENTES COM DIFERENTES FORMAS CLÍNICAS DA LEISHMANIOSE TEGUMENTAR

PALAVRAS-CHAVES:

1. Cutaneous Leishmaniasis; 2. Transcriptomic profile; 3. Nanostring; 4. RNA-seq.

PÁGINAS: 1
GRANDE ÁREA: Ciências da Saúde
ÁREA: Medicina
RESUMO:

Introduction: Cutaneous Leishmaniasis (LT) is among the six most important neglected diseases according to the World Health Organization, affecting approximately 1 to 1.5 million cases worldwide, occurring mainly in tropical and subtropical areas of the planet. In Brazil, LT has a wide distribution with case records in all regions, occurring mainly in the North and Northeast regions of the country. Vale de Jiquiriçá region, southeast region of Bahia, has the highest number of LT cases. Many studies have sought to clarify the mechanisms that control the development of the lesions and the immune response involved. High-throughput techniques have been shown to reveal important targets for disease progression, however, some immunological mechanisms have not yet been fully elucidated. It is important to identify the main factors that drive the successful establishment of Leishmania infection by directly influencing the development of different clinical forms. Thus, during infection, the host can induce immune response pathways that contribute to the resolution or favoring of the disease. More recently, the role of the Liver X Receptor pathway (LXR) has been studied in different infectious diseases, including Leishmaniasis. Objective: Our hypothesis is that differences in the gene expression profile in human LT lesions could reveal immunopathological mechanisms of LT. The general objective was to compare the genetic expression profile of molecules involved in the metabolic pathways of the localized cutaneous (LCL), disseminated (LD) and mucosal (LM) forms. Materials and methods: This is a cross-sectional study to characterize the immunopathological aspects of the lesions of patients with LCL (n = 15), LD (n = 7) and LM (n = 8) using nCounter and RNA-seq, modern and high-performance approaches to characterize the transcriptome of lesions. To evaluate the expression of LXR in the lesions, an optical microscopy analysis of immunohistochemical (IHC) -labeled tissue samples of LM, LD and healthy mucosa were performed. Results: Among the evaluated genes, 25 were positively regulated in relation to the sample of normal donors in both LCL and LM, such as ICAM-1, Caspase 1, CXCL-10 and Granzimas A and B. However, about 100 genes were only identified in LCL when compared to healthy donor skin or in LM when compared with healthy nasal mucosa. The analysis of the canonical pathways showed a positive regulation of the TREM-1 and NF-kB pathways. On the other hand, there is a negative modulation of the pathways related to LXR/RXR activation. Sequence RNA analysis of samples from 7 patients with LD and 4 healthy donors showed 1,765 genes over expressed and 384 repressed in the normal donor comparison. In IHC, LCL and LM samples showed reduction or absence of LXR positive cells while in LD there was moderate LXR labeling. Conclusion: In this way we could conclude that in LCL and LM there is activation of several proinflammatory pathways whereas in LD there is a negative modulation in the humoral and cellular immune response, as verified both at the transcriptional level and in expression of the LXR protein. On the other hand, genes capable of negatively modulating the immune response and contributing to the healing process, such as LTF and EDNRB, are regulated in LC and LD, suggesting common mechanisms of inflammation control.

MEMBROS DA BANCA:
Interno - 082.052.645-20 - ALDINA MARIA PRADO BARRAL - UFBA
Externo à Instituição - CRISTINA RIBEIRO BARROS CARDOSO
Interno - 705.619.665-91 - LEA CRISTINA DE CARVALHO CASTELLUCCI - UFBA
Externo à Instituição - NATALIA MACHADO TAVARES
Externo à Instituição - WALDEREZ ORNELAS DUTRA