Resident enteric flora modulates the development of colitis in gnotobiotic mice

Abstract

Background: Previous investigations from this laboratory have shown that infection of C3H strain mice with Brachyspira hyodysenteriae induces a typhlocolitis with features that are similar to ulcerative colitis. The immunological response of these conventional C3H/HeOuJ mice has been shown to be a predominant Thl-like response (e.g., antigen-specific IgG2a responses and IFN-y responses). While the spirochetal pathogen initiates the onset of disease, this model of bacterial-induced colitis has been shown to be dependent upon the nature of the resident bacterial flora and the host's inflammatory response. Aim: To characterize antigen-specific immune responses to a defined gastrointestinal flora in the pathogenesis of experimental colitis. Methods: Gnotobiotic C3H/HeN mice possessing an altered schaedler flora (8 separate organisms) were used to evaluate the host's response following challenge with B. hyodysenteriae. Immunologic parameters evaluated included altered cecal morphology, histologic lesion severity scores, isotype of the antigen-specific serum antibody (ELISA), and antigen-induced cytokine responses. Results: Results indicate that the onset of disease is slower and lesion severity is less in the gnotobiotic mice in comparison to C3H mice with a complex, conventional flora. The immunologic response of the gnotobiotic mice subsequent to onset of disease was of mixed Thl :Th2 phenotype, but predominantly Th2-like. Because the conventional colony of C3H mice was colonized with Helicobacter species, we co-infected the gnotobiotic C3H mice with H. bilis to assess the influence of Helicobacters on the severity of disease and the bias of the immune response. Results indicate that colonization of the gnotobiotic C3H mice with H. bilis did enhance the severity of the colonic lesions but that the immune response was shown to be Th2-like. Conclusions: These data indicate that the nature of the gastrointestinal flora significantly