Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens

• Grant number: 23/16442-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Moisés Dias de Brito
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

Leishmaniasis is an endemic disease in more than 100 countries, with over one million new cases annually. Among Latin American countries, Brazil stands out with higher disease rates, accounting for 96% of visceral leishmaniasis cases (WHO, 2018). Additionally, Leishmania amazonensis is among the circulating species in Brazil and is mainly associated with cutaneous and mucocutaneous manifestations. Therefore, it is of utmost importance to study the mechanisms by which the host's immune response controls Leishmania infection.In response to Leishmania amazonensis infection, the NLRP3 receptor-regulated inflammasome is activated. It plays a crucial role in the activation of the NLRC4 inflammasome, which induces the cleavage of Gasdermin-D. Thus, it is important to assess the role of Gasdermin-D during infection. It is worth noting that there is an intense search for molecules capable of interfering with the effector role of Gasdermin-D, which could facilitate a potential therapeutic intervention for leishmaniasis treatment. Therefore, understanding the intracellular pathways that result in pathogen control may open promising perspectives for the development of more efficient drugs in the treatment of leishmaniasis.