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

• Published in: BMC immunology Vol. 9; no. 1; p. 25
• Main Authors: Singh, Udai P, Singh, Rajesh, Singh, Shailesh, Karls, Russell K, Quinn, Frederick D, Taub, Dennis D, Lillard, James W
• Format: Journal Article
• Language: English
• Published: London BioMed Central 04.06.2008; BMC
• Subjects: Adult; Allergology; Animals; Antibodies, Bacterial - blood; Biomedical and Life Sciences; Biomedicine; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Chemokine CXCL11 - immunology; Chemokine CXCL11 - metabolism; Chemokines, CXC - immunology; Chemokines, CXC - metabolism; Colitis - immunology; Colitis - metabolism; Cytokines - immunology; Cytokines - metabolism; Cytokines and Growth Factors; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Humans; Immunology; Inflammatory Bowel Diseases - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-10 - deficiency; Interleukin-10 - immunology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Mice; Mice, Knockout; Mycobacterium avium subsp. paratuberculosis - immunology; Neutrophils - immunology; Neutrophils - metabolism; Receptors, CXCR3 - immunology; Receptors, CXCR3 - metabolism; Research Article; Serum Amyloid A Protein - analysis; Serum Amyloid A Protein - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Vaccine; Lamina Propria Lymphocyte; CXCR3 Ligand; Inflammatory Bowel Disease Patient; Mesenteric Lymph Node; Lamina Propria
• ISSN: 1471-2172; 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 -/- 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.