Banca de DEFESA: FILIPE ROCHA LIMA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : FILIPE ROCHA LIMA
DATA : 28/11/2019
HORA: 14:00
LOCAL: Auditório Aluízio Prata - IGM/FIOCRUZ
TÍTULO:

Evaluation of the immunomodulatory effect of metformin on Leishmania
braziliensis infection.

PALAVRAS-CHAVES:

Metformin. Cutaneous leishmaniasis. Diabetes. Immunomodulation.

PÁGINAS: 83
GRANDE ÁREA: Ciências Biológicas
ÁREA: Imunologia
RESUMO:

INTRODUCTION: Diabetes is classified as a risk factor for infectious and endemic diseases, in
tropical countries. The increased incidence in the severity of clinical manifestations in patients with
metabolic diseases such as T2DM is due to chronic inflammation induced by increased plasma
glucose and exogenous lipid levels. Therefore, cutaneous infections caused by pathogens in Brazil,
such as L. braziliensis (Lb), which causes cutaneous leishmaniasis (LC), represent a proposed
model to evaluate the effect of the association between DM, metformin use. Metformin is a
hypoglycemic drug of first choice for hypoglycemic treatment of DM and is widely used in the
Unified Health System (SUS), despite its interference in the host's in situ and systemic immune
response against the protozoan. Given the additional effects of metformin (MET), it is capable of
modulating the innate and adaptive host immune response. OBJECTIVE: To evaluate the
immunomodulatory effect of metformin in an experimental model of Lb infection and diabetic
patients. MATERIAL AND METHODS: This is a case-control study, convenience sample,
investigative and descriptive study in patients with LC with and without DM. Additionally, an
experimental study of Lb infection and MET treatment in vivo in BALB / c mice and in vitro in
Raw 264.7 macrophages. RESULTS: Patients with DM develop atypical LC, with less frequency
of necrosis and CD8 + T cells in lesions. MET in the in vivo experimental model induced a decrease
in serum TNF-α and IL-12p70, interfered with lesion kinetics and was associated with increased
parasite load at the inoculation site and ipsilateral lymph nodes. In MET-treated macrophages, cell
proliferation reduction was observed and there was no interference on cell viability. Small MET
concentration in L.b culture allows the maintenance of the stationary phase of growth. In vitro
infection with Lb and MET-treated cells increased the frequency of infected macrophages and
parasite load. Although MET and Lb infection alone are able to promote the production of
intracellular ROS, ROS levels are reduced in MET-treated macrophages undergoing L.b infection.
CONCLUSION: DM and MET can interfere with the phenotypic of skin lesions by modulating
cell infiltrate at the inflammation site, as well as the extent and frequency of LC necrosis in diabetic
patients. Systemically, the experimental treatment with MET was able to reduce the levels of
cytokines that induce a Th1 response, described as protective for parasitic control, as well as to
interfere with cutaneous ulceration kinetics and causing increased parasite load. Experimental
evidence was confirmed in cell culture assays in which MET increased parasitic load, altered ROS
production, and modulated cell proliferation. Based on this evidence, it can be concluded that the
use of MET worsens the evolution of cutaneous leishmaniasis and the use in diabetics in endemic
regions for LC should be evaluated.

MEMBROS DA BANCA:
Interno - 233.804.895-49 - CLAUDIA IDA BRODSKYN - UFBA
Presidente - 222.573.739-87 - SÉRGIO MARCOS ARRUDA - UFBA
Interno - 028.288.917-55 - VALÉRIA DE MATOS BORGES - UFRJ
Externo ao Programa - 2770540 - VIVIANE SAMPAIO BOAVENTURA DE OLIVEIRA