Campylobacter jejuni induces mixed Type 1 and 17 responses in a C57BL/6 IL-10−/− mouse model of colitis. (49.12)

Abstract

Abstract Campylobacter jejuni is the leading cause of food-borne enteritis and has also been linked with peripheral neuropathy and arthritis. C57BL/6 IL-10+/+ and congenic IL-10−/− mice serve as C. jejuni colonization and colitis models respectively. We hypothesized that in the absence of regulatory cytokine IL-10, uncontrolled induction of proinflammatory cytokines and infiltration of inflammatory cells is responsible for tissue obliteration in colitis. Colon cytokine analysis revealed significant time-dependent up regulation of IFN-γ, IL-17A, IL-6, TNF-α and IL-1β. A similar panel of cytokines were upregulated in the plasma and draining lymph node cultures of infected mice. Colon flow cytometric and immunohistochemical analysis revealed time-dependent increases in numbers of infiltrating macrophages, neutrophils, T cell subsets, NK cells and Thy1+ CD3- innate lymphocytes. Intra-cellular cytokine staining of colon and lymph node lymphocytes further linked IFN-γ, IL-17 and IL-22 upregulation to specific T cell subsets and innate lymphocytes. Time - dependent up regulation in anti-C. jejuni reactive IgG2b, IgG2c and IgG3, but not IgG1 or IgM were also observed in plasma of infected mice. These data demonstrate a mixed Type 1 and Type 17 induced colitis in C. jejuni 11168 challenged C57BL/6 IL-10-/- mice. Future work is directed towards understanding the relative importance of Type 1 and 17 pathways, and innate and adaptive lymphocytes in C. jejuni induced colitis.