Understanding the immune response to Leishmania infantum

• Grant number: 19/18645-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2019
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Gustavo Fernando da Silva Quirino
• 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

Abstract

Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum. The sandfly vector inoculates parasites in the skin, which disseminate to organs such as lymph nodes, spleen, liver and bone marrow, hindering the function of these organs and causing symptomatic disease. VL can be fatal if not treated. However, a large proportion of endemic individuals do not develop any disease. These individuals can be either asymptomatic - presence of cellular immune response after the Montenegro skin test but absence of disease; or endemic controls - absence of cellular immunity and symptoms. Global gene expression analysis in the peripheral blood of VL patients before and after treatment, as well as in asymptomatic and endemic controls demonstrated differencial expression of several immune response genes. These analyses allowed the comprehension of new immune effectors involved in the restriction of L. infantum in naturally infected individuals. The aim of this project is to validate and evaluate the role of differential expressed genes in samples of this cohort of individuals in experimental models. To do that, human cells will be genetically targeted for the selected genes and their function will be evaluated during infection with L. infantum. Moreover, the murine variants of the selected genes will be determined and utilized to develop genetically modified mice, which will be used as experimental models of infection with this parasite. The data generated from this project will describe new immune pathways and effectors of the immune response that account for restriction of L. infantum infection.