Evaluation of the role of inflammasome-related signaling and effector signaling pathways in the control of Leishmania amazonensis infection

• Grant number: 23/11105-0
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: CNPq
• Principal Investigator: Dario Simões Zamboni
• Grantee: Ana Patricia Cacua Gelvez
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/01560-1 - Analysis of role signaling pathways and effector molecules related to inflammasomes in the control of infection by Leishmania amazonensis, AP.R

Abstract

Leishmaniasis are a set of diseases that cause a major public health problem around the world, affecting mainly less favored individuals from emerging countries. The diseases are caused by protozoan parasites of the genus Leishmania spp., presenting different known clinical forms: cutaneous, mucocutaneous and visceral. In the mammalian host, these parasites preferentially infect phagocytic cells, mainly macrophages and dendritic cells of the innate immune system, which play an important role in the elimination of intracellular pathogens. The parasite Leishmania amazonensis is the main etiological agent of human tegumentary leishmaniasis in the Americas, with a reduced immune response in infected patients, generally developing a Th2 type response against the infection, with the presence of high levels of anti-inflammatory cytokines, favoring the development the infection and therefore the disease. These diseases are considered neglected and, despite being curable, affect around 850,000 people a year worldwide. Our group demonstrated that the NLRP3 inflammasome plays an important role in the development and clinical outcome of Leishmaniasis. Activation of inflammasomes leads to the production of inflammatory cytokines, including IL-1² and IL-1±, which signal through the IL1R receptor. In the present proposal, we intend to investigate the contribution and the IL-1± and IL-1²-dependent signaling pathways involved in the control of the infection, as well as their release by NLRP3-independent inflammasomes, including AIM2 and NLRC4. Our results will contribute to a better understanding of cellular responses associated with the control of infections by Leishmania spp., as well as to identify processes by which the host fights infections.