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Infect. Immun. doi:10.1128/IAI.01770-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influence of Mycobacterium avium paratuberculosis on colitis development and specific immune responses during disease

Udai P. Singh, Shailesh Singh, Rajesh Singh, Russell K. Karls, Frederick D. Quinn, Morris E. Potter, and James W. Lillard Jr.*

Department of Microbiology and Immunology, Morehouse School of Medicine; Department of Microbiology & Immunology, University of Louisville; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia; Center for Food Safety and Applied Nutrition, Food and Drug Administration

* To whom correspondence should be addressed. Email: james.lillard{at}louisville.edu.


   Abstract

The granulomatous and intramural inflammation observed in cases of inflammatory bowel diseases (IBD) and veterinary Johne's disease suggests Mycobacterium avium paratuberculosis (MAP) via contaminated dairy products is a causative agent. However, an incomplete understanding of the immunological steps responsible for the pathologies of IBD makes this conclusion uncertain. Serum from IL-10-/- mice with spontaneous colitis displayed significantly higher MAP-specific IgG2a Ab responses than serum from similar mice without disease. Pathogen free IL-10-/- mice received control vehicle or the vehicle containing heat-killed or live MAP. Mucosal CD4+ T cells from these mice that developed colitis proliferated and secreted higher levels of IFN-{gamma} and TNF-{alpha} after ex vivo stimulationith a V{beta}11+ TCR-restricted peptide from the MPT59/85B antigen (Ag), compared with cells from mice before the onset of colitis. The data from this study provide important information regarding the mechanisms of colitis in IL-10-/- mice driven in part by Ag85B-specific T cells. The data suggest a plausible mechanism of Ag-specific T cell responses in colitis driven by potent Ags conserved in Mycobacterium species.







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