Identification and validation of essential genes responsible for the immune response induction in patients with visceral leishmaniasis

• Grant number: 15/25289-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2016
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Gabriela Pessenda
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 17/09746-6 - The role of dermal macrophages in the initial immune response against Leishmania infection, BE.EP.DR

Abstract

Leishmaniasis affects about 12 million people worldwide and includes diseases ranging from the localized cutaneous form to the visceral one, which is the most severe manifestation, with high human mortality and morbidity. Visceral leishmaniasis (VL) is mainly characterized by a chronic inflammatory response, and although it is a result of a change in the balance of effector and regulatory factors, the understanding (s) of the immune (s) mechanism (s) that contribute to the disease pathophysiology is still restricted. 85% of patients with VL are asymptomatic for the disease, whereas symptomatic patients may present few to severe clinical symptoms. It is possible that these different responses are associated with distinct gene expression profiles resulting in diverse immune responses. Based on the above, our goal is to validate differentially expressed genes between different groups of patients with LV, which include the symptomatic patients before and after treatment, and asymptomatic controls. We will employ the methodology of in vitro transfection of cells, to increase or decrease the expression of genes of interest, and evaluate the potential effects of these selected genes in the immune system responses to infection. In vivo models of infection using knockout animals may also be employed. Our goal will also be to evaluate the differential genes expression of inflamassomes in patients, and validate them in order to understand their role during infection by L. infantum in humans. It is expected that the results could contribute to the discovery of therapeutic targets and important biomarkers for the treatment and prognosis of the disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PESSENDA, GABRIELA; DA SILVA, JOAO SANTANA. Arginase and its mechanisms inLeishmaniapersistence. PARASITE IMMUNOLOGY, v. 42, n. 7, SI, JUL 2020. (17/09746-6, 15/25289-9)