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Helicobacter bilis triggers persistent immune reactivity to antigens derived from the commensal bacteria in gnotobiotic C3H/HeN mice
  1. Albert E Jergens (ajergens{at}
  1. Iowa State University, United States
    1. Jenny Wilson-Welder
    1. Iowa State University, United States
      1. Andrea Dorn
      1. Iowa State University, United States
        1. Abigail Henderson
        1. Iowa State University, United States
          1. Zhiping Liu
          1. Iowa State University, United States
            1. Richard Evans
            1. Iowa State University, United States
              1. Jesse Hostetter
              1. Iowa State University, United States
                1. Michael Wannemuehler
                1. Iowa State University, United States


                  Background: Infection with Helicobacter species has been associated with the development of mucosal inflammation and inflammatory bowel disease (IBD) in several mouse models. However, consensus regarding the role of Helicobacter as a model organism to study microbial-induced IBD is confounded by the presence of a complex colonic microbiota.

                  Aim: To investigate the kinetics and inflammatory effects of immune system activation to commensal bacteria following H. bilis colonization in gnotobiotic mice.

                  Methods: C3H/HeN mice harboring an altered Schaedler flora were selectively colonized with H. bilis and host responses were investigated over a 10 week period. Control mice were colonized only with the defined flora. Tissues were analyzed for gross/histopathologic lesions and bacterial antigen-specific antibody and T cell responses.

                  Results: Gnotobiotic mice colonized with H. bilis developed mild macro- and microscopic lesions of typhlocolitis beginning 3 weeks post-infection. ASF-specific IgG responses were demonstrable within 3 weeks, persisted throughout the 10 week study, and presented as a mixed IgG1:IgG2a profile. Lymphocytes recovered from the mesenteric lymph node of H. bilis-colonized mice produced increased levels of IFN-γ, TNF-α, IL-6, and IL-12 in response to stimulation with commensal- or H. bilis-specific bacterial lysates. In contrast, defined flora mice not colonized with H. bilis did not develop immune responses to their resident flora and remained disease free.

                  Conclusions: Colonization of gnotobiotic C3H/HeN mice with H. bilis perturbs the host's response to its resident flora and induces progressive immune reactivity to commensal bacteria that contributes to the development of immune-mediated intestinal inflammation.

                  • IBD
                  • altered Schaedler flora
                  • bacterial provocateur
                  • gnotobiotic

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