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

SC Kim, SL Tonkonogy, T Karrasch… - Inflammatory bowel …, 2007 - academic.oup.com
SC Kim, SL Tonkonogy, T Karrasch, C Jobin, BR Sartor
Inflammatory bowel diseases, 2007academic.oup.com
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) …
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-γ 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-κB was activated in the duodenum and colon in dual-associated IL-10−/− × NF-κBEGFP 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.
Oxford University Press