The involvement of poly(ADP-Ribose)polymerase-1 enzyme on iNOS expression by Naip5/NLRC4-caspase-1 axis

• Grant number: 12/21317-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2013
• End date: May 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Karina Ramalho Bortoluci
• Grantee: Carina Buzzo de Lima
• Supervisor: Michael O. Hottiger
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Zurich (UZH), Switzerland
• Associated to the scholarship: 09/16966-6 - Molecular Pathways involved in cytosolic flagellin-induced iNOS expression: Consequences for macrophage resistance against infections., BP.DR

Abstract

The discovery of two large families of receptors that recognize a range of molecular patterns associated with pathogens, was of great importance for the understanding of recognition mechanisms mediated by innate immunity cells. These two families which include the transmembrane Toll-like receptors (TLRs) and cytoplasmic receptors, NOD-like receptors (NLRs), although induce distinct responses to pathogen control, can share the same ligant. Accordingly, the recognition of flagellin, the monomeric subunit of flagella present in motile bacteria, is shared by the transmembrane receptor TLR5 seems to recognize that all motile bacteria, and the cytosolic receptors, Naip5|NLRC4, which only seem to recognize invasive bacteria. Thus, a major challenge of innate immunity is to understand the relative contribution of different types of receptors for molecular patterns in resistance against pathogens and activation of specific immune response. As an object of study of PhD project (Process No. 2009/16966-6) investigated the role of these receptors in the activation of macrophages, emphasizing the microbicidal capacity of these cells. In this sense, we describe a novel pathway of activation of iNOS-dependent of Naip5 | NLRC4-caspase-1, independent of MyD88 in response to cytosolic flagellin. The activation of iNOS by Naip5 | NLRC4-caspase-1 axis is involved in the control of infection by Legionella pneumophila and Salmonella typhimurium by macrophages. However, the molecular mechanisms involved in the interaction between caspase-1 and iNOS still require elucidation, this project proposal Bepe. (AU)