Friday, October 28, 2011
Hall 1-2 (San Jose Convention Center)
Flagellin has been associated with virulence, systemic infection, persistence and inflammation in several pathogenic microbes including S. typhimurium and Pseudomonas. Flagellin is also a target of the innate immune system, and flagellin induces potent immune responses. Toll-like receptor 5 (TLR-5) recognizes extracellular flagellin leading to the activation of NF-kB. Recognition of cytosolic flagellin by Naip5 leads to activation of the inflammasome via IPAF and caspase-1, leading to secretion of IL-1B and cell death. However, the functional significance of each of the two independent flagellin recognition systems in innate immunity to Salmonella infection is unknown. FlgM, a negative regulator of the flagellar apparatus, has drawn our attention as a potential candidate that would allow us to assess the importance of each flagellin recognition site. Salmonella typhimurium deficient in FlgM show an attenuated in vivo phenotype which we attribute to an aberrant overexpression of its flagellar genes, leading to a better recognition and clearance by the host. We plan to generate mutant versions of flagellin that disrupt its recognition sites, introduce it in our overexpressing flagellin mutant (FlgM), and study the impact of each recognition site in virulence, inflammation and infection. Alternatively, we plan to use TLR5 KO and caspase 1 KO mice to study the role of each pathway from a host perspective. My goals are to determine the role of each of the two innate immune recognition systems for bacterial flagellin against Salmonella infection.