Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria.
OBJECTIVE
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.
Kim
Sandra C
SC
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC 27599-7032, USA.
Tonkonogy
Susan L
SL
Albright
Carol A
CA
Tsang
Julia
J
Balish
Edward J
EJ
Braun
Jonathon
J
Huycke
Mark M
MM
Sartor
R Balfour
RB
D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002429:Cecal Diseases / Q000382:microbiology / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D013293:Enterococcus faecalis / Q000276:immunology; D004760:Enterocolitis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000382:microbiology; D005759:Gastroenteritis / Q000382:microbiology / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D016753:Interleukin-10 / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D000942:Antigens, Bacterial; D016207:Cytokines; D016753:Interleukin-10