Identification of new molecules in macrophages involved in inflammasome activation in response to intracellular pathogens

• Grant number: 17/04242-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2017
• End date: March 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Augusto Velozo Gonçalves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion, AP.TEM

Abstract

Innate immunity plays roles in many processes during the response against pathogens, including the first contact with the invading microorganisms. In this process, Pattern Recognition Receptors (PRRs) are responsible for detection of Pathogen- and Damage-associated Molecular Patterns (PAMPs and DAMPs) present during an infection. Some families of cytosolic PRRs are involved in the assembly of inflammasomes, proteinaceous platforms that promote maturation of inflammatory caspases and consequently induce pyroptosis and maturation of proinflammatory cytokines. The inflammasomes have been implicated in the detection of many ligands such as lipopolysaccharide, flagellin, double-stranded DNA, peptidoglycan sub products and others, but many of the PAMPs and DAMPs recognition mechanisms and signalling pathways downstream of activation remain undescribed. This project proposes a genomic screen in macrophages using a CRISPR/Cas9-based system in order to identify novel molecules that take part in the activation of inflammassomes triggered by a Legionella infection model, thus contributing to the understanding of the molecular mechanisms associated to the response against intracellular pathogens. (AU)