Evaluation of caspase-8 activity regulation by caspase-1 in response to Legionella pneumophila infection

• Grant number: 16/24050-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2016
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Victor Hugo Calegari de Toledo
• 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

The Gram-negative bacteria Legionella pneumophila causes Pontiac fever and Legionnaires' disease. Transmitted by contaminated water droplets, it infects alveolar macrophages and disrupts their cellular processes responsible for pathogen clearance. One of the virulence factors of L. pneumophila, the Dot/Icm secretion system functions as a needle for virulence protein injection, establishing a protected vacuole where the bacteria replicates. Some of these proteins are sensed by pattern recognition receptors (PRRs), molecules that initiate innate immune responses that restrict bacterial replication. Preliminary studies from our group demonstrated that an inflammasome activation pathway is triggered only in the absence of caspase-1 and depends on NLRC4, ASC, flagellin and caspase-8. Thereby, this project aims to evaluate caspase-8 activity regulation by caspase-1 in order to expand our knowledge about intracellular pathways responsible for the response to Legionella pneumophila infection. Studying bacterial virulence mechanisms and the subsequent host cell response unravels new possibilities of understanding related diseases progression. (AU)