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


OBJECTIVE
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 gamma, tumour necrosis factor alpha (TNFalpha), 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.
Jergens
Albert E
AE
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. ajergens@iastate.edu
Wilson-Welder
Jennifer H
JH
Dorn
Andrea
A
Henderson
Abigail
A
Liu
Zhiping
Z
Evans
Richard B
RB
Hostetter
Jesse
J
Wannemuehler
Michael J
MJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005856:Germ-Free Life; D016998:Helicobacter / Q000276:immunology*; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction / Q000379:methods; D013559:Symbiosis
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G