CXCL10 super(+ )T cells and NK cells assist in the recruitment and activation of CXCR3 super(+ )and CXCL11 super(+ )leukocytes during Mycobacteria-enhanced colitis

• Published in: BMC immunology 2008-01, Vol.9, p.25-25
• Main Authors: Singh, Udai P, Singh, Rajesh, Singh, Shailesh, Karls, Russell K, Quinn, Frederick D, Taub, Dennis D, Lillard, James W
• Format: Article
• Language: English
• Subjects: Mycobacterium avium
• ISSN: 1471-2172
• DOI: 10.1186/1471-2172-9-25

Background The role of Mycobacteria in the etiology of Crohn's disease (CD) has been a contentious subject for many years. Recently, our laboratory showed that spontaneous colitis in IL-10 super(-/- )mice is driven in part by antigens (Ags) conserved in Mycobacteria. The present study dissects some of the common cellular and molecular mechanism that drive Mycobacteria-mediated and spontaneous colitis in IL-10 super(-/- )mice. Results We show that serum from inflammatory bowel disease (IBD) patients contain significantly higher levels of Mycobacterium avium paratuberculosis-specific IgG1 and IgG2 antibodies (Abs), serum amyloid A (SAA) as well as CXCR3 ligands than serum from healthy donors. To study the cellular mechanisms of Mycobacteria-associated colitis, pathogen-free IL-10 super(-/- )mice were given heat-killed or live M. avium paratuberculosis. The numbers of mucosal T cells, neutrophils, NK/NKT cells that expressed TNF alpha , IFN- gamma , and/or CXCL10 were significantly higher in mice that received live Mycobacteria than other groups. The numbers of mucosal CXCR3 super(+), CXCL9 super(+), CXCL11 super(+ )and/or IFN- gamma super(+ )dendritic cells (DCs) were also significantly higher in M. avium paratuberculosis-challenged mice, than compared to control mice. Conclusion The present study shows that CD and UC patients mount significant Mycobacteria-specific IgG1 > IgG2 and CXCR3 ligand responses. Several cellular mechanisms that drive spontaneous colitis also mediate Mycobacteria-enhanced colitis in IL-10 super(-/- )mice. Similar to IL-10 super(-/- )mice under conventional housing, we show that Mycobacteria-challenge IL-10 super(-/- )mice housed under otherwise pathogen-free conditions develop colitis that is driven by CXCR3- and CXCR3 ligand-expressing leukocytes, which underscores another important hallmark and molecular mechanism of colitis. Together, the data show that Mycobacteria-dependent host responses, namely CXCL10 super(+ )T cells and NK cells, assist in the recruitment and activation of CXCR3 super(+ )and CXCL11 super(+ )leukocytes to enhance colitis of susceptible hosts.