Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9245478 | Gastroenterology | 2005 | 16 Pages |
Abstract
Background & Aims: To explore the hypothesis that selective immune responses to distinct components of the intestinal microflora induce intestinal inflammation, we characterized disease kinetics and bacterial antigen-specific T-cell responses in ex germ-free interleukin 10â/â and wild-type control mice monoassociated with Enterococcus faecalis, Escherichia coli, or Pseudomonas fluorescens. Methods: Colitis was measured by using blinded histological scores and spontaneous interleukin 12 secretion from colonic strip culture supernatants. Interferon γ secretion was measured from mesenteric or caudal lymph node CD4+ T cells stimulated with bacterial lysate-pulsed antigen-presenting cells. Luminal bacterial concentrations were measured by culture and quantitative polymerase chain reaction. Results:Escherichia coli induced mild cecal inflammation after 3 weeks of monoassociation in interleukin 10â/â mice. In contrast, Enterococcus faecalis-monoassociated interleukin 10â/â mice developed distal colitis at 10-12 weeks that was progressively more severe and associated with duodenal inflammation and obstruction by 30 weeks. Neither bacterial strain induced inflammation in wild-type mice, and germ-free and Pseudomonas fluorescens-monoassociated interleukin 10â/â mice remained disease free. CD4+ T cells from Enterococcus faecalis- or Escherichia coli-monoassociated interleukin 10â/â mice selectively produced higher levels of interferon γ and interleukin 4 when stimulated with antigen-presenting cells pulsed with the bacterial species that induced disease; these immune responses preceded the onset of histological inflammation in Enterococcus faecalis-monoassociated mice. Luminal bacterial concentrations did not explain regional differences in inflammation. Conclusions: Different commensal bacterial species selectively initiate immune-mediated intestinal inflammation with distinctly different kinetics and anatomic distribution in the same host.
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Authors
Sandra C. Kim, Susan L. Tonkonogy, Carol A. Albright, Julia Tsang, Edward J. Balish, Jonathon Braun, Mark M. Huycke, R. Balfour Sartor,