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dc.contributor.authorSingh, Udai P
dc.contributor.authorSingh, Rajesh
dc.contributor.authorSingh, Shailesh
dc.contributor.authorKarls, Russell K
dc.contributor.authorQuinn, Frederick D
dc.contributor.authorTaub, Dennis D
dc.contributor.authorLillard, James W Jr
dc.date.accessioned2013-06-12T15:12:18Z
dc.date.available2013-06-12T15:12:18Z
dc.date.issued2008-06-04
dc.identifier.citationBMC Immunology. 2008 Jun 04;9(1):25
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2172-9-25
dc.identifier.urihttp://hdl.handle.net/10724/19730
dc.description.abstractAbstract 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-/- 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-/- 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-/- mice were given heat-killed or live M. avium paratuberculosis. 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 Mycobacteria than other groups. The numbers of mucosal CXCR3+, CXCL9+, CXCL11+ and/or IFN-γ+ 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-/- mice. Similar to IL-10-/- mice under conventional housing, we show that Mycobacteria-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 Mycobacteria-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.
dc.titleCXCL10+ T cells and NK cells assist in the recruitment and activation of CXCR3+ and CXCL11+ leukocytes during Mycobacteria-enhanced colitis
dc.typeJournal Article
dc.date.updated2013-06-07T18:47:49Z
dc.description.versionPeer Reviewed
dc.language.rfc3066en
dc.rights.holderUdai P Singh et al.; licensee BioMed Central Ltd.


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