Evaluation of Naip receptors in NLRC4 inflammasome activation in response to L. amazonensis infection

• Grant number: 18/10444-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2018
• Effective date (End): November 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Victoria Maria dos Santos
• 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

Pattern recognition receptors (PRR) are responsible for recognition of molecular patterns MAMPs or DAMPs. NLRs are a group of intracellular receptors that recognize endogenous and exogenous danger signals and participate of the inflammasome formation. The inflammasome is able to activate inflammatory caspases, such as caspase-1 that is responsible for processing and secretetion of IL-1² and IL-18, as well to induce an inflammatory form of cell death called pyroptosis. Leishmaniasis is a group of diseases caused by protozoa of Leishmania genus. These parasites exhibit a remarkable capacity to survive and proliferate within the phagolysosome of host macrophages. Macrophages are critical for effective and protective immune responses to different diseases, including Leishmaniasis. Recently we found that NLRC4 is activated in response to L. amazonensis infection and plays an important role in controlling infection in macrophages and in vivo. Our results sugest that NLRC4 is involved in the activation of NLRP3 inflammasome in response to L. amazonensis infection induced by pore formation and potassium efflux. Thus, the aim of this work is evaluate the involvement of NAIPs (NAIP1, NAIP2 e NAIP5) receptors in NLRC4 inflammasome activation in response to infection by L. amazonensis.