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


OBJECTIVE
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.


CONCLUSIONS
Two commensal bacteria that individually induce phenotypically distinct colitis in gnotobiotic IL-10-/- mice act additively to induce aggressive pancolitis and duodenal inflammation.
Kim
Sandra C
SC
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. skim@med.unc.edu
Tonkonogy
Susan L
SL
Karrasch
Thomas
T
Jobin
Christian
C
Sartor
R Balfour
RB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000382:microbiology*; D003106:Colon / Q000737:chemistry / Q000473:pathology; D015169:Colony Count, Microbial; D004382:Duodenitis / Q000276:immunology / Q000382:microbiology; D013293:Enterococcus faecalis / Q000254:growth & development*; D004926:Escherichia coli / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005856:Germ-Free Life; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000172:deficiency*; D018664:Interleukin-12 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000096:biosynthesis; D015854:Up-Regulation
D053759:Interleukin-23; D016328:NF-kappa B; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma