Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria

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 10 −/− 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 10 −/− mice. In contrast, Enterococcus faecalis–monoassociated interleukin 10 −/− 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 10 −/− mice remained disease free. CD4 + T cells from Enterococcus faecalis– or Escherichia coli–monoassociated interleukin 10 −/− 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.