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Inflamm Bowel Dis. 2007 Dec;13(12):1457-66.

Dual-association of gnotobiotic IL-10-/- mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis.

Author information

1
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. skim@med.unc.edu

Abstract

BACKGROUND:

Monoassociating gnotobiotic IL-10-deficient (-/-) mice with either nonpathogenic Enterococcus faecalis or a nonpathogenic Escherichia coli strain induces T-cell-mediated colitis with different kinetics and anatomical location (E. faecalis: late onset, distal colonic; E. coli: early onset, cecal).

HYPOTHESIS:

E. faecalis and E. coli act in an additive manner to induce more aggressive colitis than disease induced by each bacterial species independently.

METHODS:

Germ-free (GF) inbred 129S6/SvEv IL-10-/- and wildtype (WT) mice inoculated with nonpathogenic E. faecalis and/or E. coli were killed 3-7 weeks later. Colonic segments were scored histologically for inflammation (0 to 4) or incubated in media overnight to measure spontaneous IL-12/IL-23p40 secretion. Bacterial species were quantified by serial dilution and plated on culture media. Mesenteric lymph node (MLN) CD4(+) cells were stimulated with antigen-presenting cells pulsed with bacterial lysate (E. faecalis, E. coli, Bacteroides vulgatus) or KLH (unrelated antigen control). IFN-gamma and IL-17 levels were measured in the supernatants.

RESULTS:

Dual-associated IL-10-/- (but not WT) mice developed mild-to-moderate pancolitis by 3 weeks that progressed to severe distal colonic-predominant pancolitis with reactive atypia and duodenal inflammation by 7 weeks. NF-kappaB was activated in the duodenum and colon in dual-associated IL-10-/- x NF-kappaB(EGFP) mice. The aggressiveness of intestinal inflammation and the degree of antigen-specific CD4(+) cell activation were greater in dual- versus monoassociated IL-10-/- mice.

CONCLUSION:

Two commensal bacteria that individually induce phenotypically distinct colitis in gnotobiotic IL-10-/- mice act additively to induce aggressive pancolitis and duodenal inflammation.

PMID:
17763473
DOI:
10.1002/ibd.20246
[Indexed for MEDLINE]

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