Mechanism underlying immune-modulatory effects of LcrV

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DESCRIPTION (provided by applicant): LcrV is a 37kDa multi-functional virulence protein produced by all three pathogenic Yersinia species. LcrV is well known for its immune-modulatory function which may exploit toll-like pathway to induce IL-10; however, preliminary studies demonstrate that IL-10, though required, is not sufficient for immune-suppression. Our data suggests that there is a novel mechanism involved in immune mediated suppression by LcrV mediated by TLR2/CD14. This proposal will focus on characterizing and exploring the interactions of LcrV with APCs and the TLR system. (1) Comparison of LcrV and LcrV deletion mutants on stimulating APC populations. (2) Fully characterize the immune suppression mediated by LcrV. (3) Determine the additional molecular events needed for the immune-suppression mediated by LcrV. Understanding the molecular mechanism underlying LcrV mediated immune modulation will not only give better insight into microbial pathogenesis and vaccine development, but also have implications on the of TLR signaling in IL-10- mediated immune-suppression.