Mechanism underlying immune-modulatory effects of LcrV

描述（由申请方提供）：LcrV是一种37 kDa的多功能毒力蛋白，由所有三种致病性耶尔森氏菌属产生。众所周知，LcrV具有免疫调节功能，可利用toll样途径诱导IL-10;然而，初步研究表明，IL-10虽然是必需的，但不足以抑制免疫。我们的数据表明，有一个新的机制，参与免疫介导的抑制LcrV介导的TLR 2/CD 14。该提案将集中于表征和探索LcrV与APC和TLR系统的相互作用。(1)LcrV和LcrV缺失突变体对刺激APC群体的比较。(2)充分表征LcrV介导的免疫抑制。(3)确定LcrV介导的免疫抑制所需的其他分子事件。了解LcrV介导的免疫调节的分子机制不仅可以更好地了解微生物发病机制和疫苗开发，而且还对IL-10介导的免疫抑制中的TLR信号传导具有影响。

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.