This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01770-06v1 75/8/3722    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Singh, U. P. Articles by Lillard, J. W. Search for Related Content PubMed PubMed Citation Articles by Singh, U. P. Articles by Lillard, J. W., Jr.

Influence of Mycobacterium avium subsp. paratuberculosis on Colitis Development and Specific Immune Responses during Disease

Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia,¹ Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky,² Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia,³ Center for Food Safety and Applied Nutrition, Food and Drug Administration, Atlanta, Georgia⁴

Received 6 November 2006/ Returned for modification 4 January 2007/ Accepted 3 May 2007

The granulomatous and intramural inflammation observed in cases of inflammatory bowel diseases (IBD) and veterinary Johne's disease suggests that Mycobacterium avium subsp. paratuberculosis is a causative agent. However, an incomplete understanding of the immunological steps responsible for the pathologies of IBD makes this conclusion uncertain. Sera from interleukin-10-deficient (IL-10^–/–) mice with spontaneous colitis displayed significantly higher M. avium subsp. paratuberculosis-specific immunoglobulin G2a antibody responses than did sera from similar mice without disease. Pathogen-free IL-10^–/– mice received control vehicle or the vehicle containing heat-killed or live M. avium subsp. paratuberculosis. Mucosal CD4⁺ T cells from the mice that developed colitis proliferated and secreted higher levels of gamma interferon and tumor necrosis factor alpha after ex vivo stimulation with a Vß11⁺ T-cell receptor-restricted peptide from the MPT59 antigen (Ag85B) than those secreted from 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, which are 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.

Published ahead of print on 14 May 2007.

Editor: J. L. Flynn