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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 Jergens1,
  2. Jennifer H Wilson-Welder2,
  3. Andrea Dorn2,
  4. Abigail Henderson2,
  5. Zhiping Liu2,
  6. Richard B Evans3,
  7. Jesse Hostetter4,
  8. Michael J Wannemuehler2
  1. 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
  2. 2Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
  3. 3Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
  4. 4Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
  1. Correspondence to:
    A E Jergens
    Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA; ajergens{at}iastate.edu

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 γ, tumour necrosis factor α (TNFα), 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.

  • ASF, altered Schaedler flora
  • DF, defined flora
  • ELISA, enzyme-linked immunosorbent assay
  • FBS, fetal bovine serum
  • IBD, inflammatory bowel disease
  • IFNγ, interferon γ
  • IL, interleukin
  • MLN, mesenteric lymph node
  • NI, non-infected
  • PBS, phophate-buffered saline
  • PBST, phosphate-buffered saline Tween 20
  • PI, postinfection
  • SPF, specific pathogen-free
  • SPL, spleen

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Footnotes

  • Published Online First 1 December 2006

  • Competing interests: None declared.

  • Funding: This work was supported by NIH grant KO1 RR 018618 (NCRR).

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