Helicobacter bilis triggers persistent immune reactivity to antigens derived from the commensal bacteria in gnotobiotic C3H/HeN mice

Abstract

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 colonisation in gnotobiotic mice. Methods: C3H/HeN mice harbouring an altered Schaedler flora (ASF) were selectively colonised with H bilis and host responses were investigated over a 10-week period. Control mice were colonised only with the defined flora (DF). Tissues were analysed for gross/histopathological lesions, and bacterial antigen-specific antibody and T-cell responses. Results: Gnotobiotic mice colonised with H bilis developed mild macroscopic and microscopic lesions of typhlocolitis beginning 3 weeks postinfection. 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-colonised mice produced increased levels of interferon c, tumour necrosis factor a (TNFa), interleukin 6 (IL6) and IL12 in response to stimulation with commensal-or H bilis-specific bacterial lysates. In contrast, DF mice not colonised with H bilis did not develop immune responses to their resident flora and remained disease free. Conclusions: Colonisation 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.

Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

“…Previous work from our laboratory has demonstrated that H. bilis colonization induces host immune responses against antigens derived from the resident microbiota and alters the mucosal gene expression profiles in immunocompetent mice, yet these mice fail to develop severe colitis [17][18][19]. These results suggest that the introduction of a bacterial provocateur such as H. bilis may disrupt mucosal homeostasis and subsequently increase the host's susceptibility to IBD following an inflammatory event.…”

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract

“…Helicobacter species that can survive in, or colonise, the bile ducts may induce the formation of gallstones both directly, through the urease activity of some of the species, or indirectly through a T-cell-dependent immune response (Belzer et al, 2006;Maurer et al, 2007). The colonisation of the mucosa by bacteria may also aggravate the chronic inflammatory state already caused by gallstones (Wistuba and Gazdar, 2004;Jergens et al, 2007). In animal studies, the sequence of events going from chronic inflammation to cancer has been directly linked to some Helicobacter species.…”

The Family Helicobacteraceae

“…It has also been recently detected in aged hamsters diagnosed with a range of hepato-biliary diseases including hepatitis, hepatic dysplasia and biliary hyperplasia ). Although the role of H. bilis in the above diseases and IBD requires clarification it has been suggested that H. bilis may be capable of altering the host's response to its own microbiota that could result in intestinal inflammation (Jergens et al 2007). The recent reclassification of a number of the flexispira organisms as H. bilis s.s. (Hanninen et al 2005;Rossi et al 2010) has not only expanded their host range but has also identified it as a pathogen capable of inducing abortion in sheep (natural and experimental infections) and experimentally infected guinea pigs (Kirkbride et al 1985(Kirkbride et al , 1986Bryner et al 1987).…”