Dual-association of gnotobiotic Il-10-/- mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis.
Kim, Sandra C. MD 1*; Tonkonogy, Susan L. PhD 2; Karrasch, Thomas MD 1; Jobin, Christian PhD 1; Sartor, Balfour R. MD 1
Inflammatory Bowel Diseases.
13(12):1457-1466, December 2007.
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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-[kappa]B was activated in the duodenum and colon in dual-associated IL-10-/- x NF-[kappa]BEGFP 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.
(Inflamm Bowel Dis 2007)
(C) Crohn's & Colitis Foundation of America, Inc.