CXCL10⁺T cells and NK cells assist in the recruitment and activation of CXCR3⁺and CXCL11⁺leukocytes during <it>Mycobacteria</it>-enhanced colitis

• Main Authors: Quinn Frederick D, Karls Russell K, Singh Shailesh, Singh Rajesh, Singh Udai P, Taub Dennis D, Lillard James W
• Format: Article
• Language: English
• Published: BMC 2008-06-01
• Series: BMC Immunology
• Online Access: http://www.biomedcentral.com/1471-2172/9/25
• ISSN: 1471-2172

<p>Abstract</p> <p>Background</p> <p>The role of <it>Mycobacteria </it>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^-/-mice is driven in part by antigens (Ags) conserved in <it>Mycobacteria</it>. The present study dissects some of the common cellular and molecular mechanism that drive <it>Mycobacteria</it>-mediated and spontaneous colitis in IL-10^-/-mice.</p> <p>Results</p> <p>We show that serum from inflammatory bowel disease (IBD) patients contain significantly higher levels of <it>Mycobacterium avium paratuberculosis</it>-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 <it>Mycobacteria</it>-associated colitis, pathogen-free IL-10^-/-mice were given heat-killed or live <it>M. avium paratuberculosis</it>. The numbers of mucosal T cells, neutrophils, NK/NKT cells that expressed TNFα, IFN-γ, and/or CXCL10 were significantly higher in mice that received live <it>Mycobacteria </it>than other groups. The numbers of mucosal CXCR3⁺, CXCL9⁺, CXCL11⁺and/or IFN-γ⁺dendritic cells (DCs) were also significantly higher in <it>M. avium paratuberculosis</it>-challenged mice, than compared to control mice.</p> <p>Conclusion</p> <p>The present study shows that CD and UC patients mount significant <it>Mycobacteria</it>-specific IgG1 > IgG2 and CXCR3 ligand responses. Several cellular mechanisms that drive spontaneous colitis also mediate <it>Mycobacteria</it>-enhanced colitis in IL-10^-/-mice. Similar to IL-10^-/-mice under conventional housing, we show that <it>Mycobacteria</it>-challenge IL-10^-/-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 <it>Mycobacteria</it>-dependent host responses, namely CXCL10⁺T cells and NK cells, assist in the recruitment and activation of CXCR3⁺and CXCL11⁺leukocytes to enhance colitis of susceptible hosts.</p>