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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI068370-02
Application #
7303772
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Mukhopadhyay, Suman
Project Start
2006-07-01
Project End
2007-07-31
Budget Start
2007-07-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$4,202
Indirect Cost
Name
University of Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Depaolo, R William; Tang, Fangming; Kim, Inyoung et al. (2008) Toll-like receptor 6 drives differentiation of tolerogenic dendritic cells and contributes to LcrV-mediated plague pathogenesis. Cell Host Microbe 4:350-61