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. 2005 Apr;128(4):891-906.
doi: 10.1053/j.gastro.2005.02.009.

Variable Phenotypes of Enterocolitis in Interleukin 10-deficient Mice Monoassociated With Two Different Commensal Bacteria

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Variable Phenotypes of Enterocolitis in Interleukin 10-deficient Mice Monoassociated With Two Different Commensal Bacteria

Sandra C Kim et al. Gastroenterology. .

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 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 gamma 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 gamma 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.

Comment in

  • Commensal flora: wolf in sheep's clothing.
    Xavier R, Podolsky DK. Xavier R, et al. Gastroenterology. 2005 Apr;128(4):1122-6. doi: 10.1053/j.gastro.2005.02.053. Gastroenterology. 2005. PMID: 15825094 Review. No abstract available.

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