Influence of Mycobacterium avium subsp. paratuberculosis on colitis development and specific immune responses during disease.
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 Vbeta11(+) 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.
Singh
Udai P
UP
Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, 580 S. Preston Street, Baxter II/Room 304C, Louisville, KY 40202, USA.
Singh
Shailesh
S
Singh
Rajesh
R
Karls
Russell K
RK
Quinn
Frederick D
FD
Potter
Morris E
ME
Lillard
James W
JW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency; D007413:Intestinal Mucosa / Q000276:immunology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010283:Paratuberculosis / Q000276:immunology* / Q000473:pathology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D007074:Immunoglobulin G; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C522414:antigen 85B, Mycobacterium paratuberculosis; D016753:Interleukin-10; D007371:Interferon-gamma