title: The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5.
abstract: BACKGROUND
  Inflammatory bowel diseases (IBDs) appear to be modulated by the interaction of pathogen-associated molecular patterns (PAMPs) derived from intestinal bacteria with their respective innate immune receptors, including Toll-like receptors (TLRs). We aimed to establish if intestinal concentrations of proinflammatory bacterial ligands of TLR2, TLR4, or TLR5 may be altered in murine IBD models, and to characterize which of the major bacterial groups may contribute to each signal.
  
  
  RESULTS
  PAMPs specific for TLR2 (lipopeptide equivalents), TLR4 (lipopolysaccharide equivalents), and TLR5 (flagellin equivalents) in human and murine fecal and intestinal samples were quantified using HEK-293 cells transfected with respective TLRs and calibrated with defined standard PAMPs. The induction of colitis in mice by dextran-sodium-sulphate treatment significantly increased colonic lipopeptide (fourfold) and LPS equivalent (550-fold) concentrations, while flagellin equivalent concentrations remained similar. The induction of ileitis by oral infection with Toxoplasma gondii dramatically increased ileal concentrations of lipopeptide (370-fold), LPS (3,300-fold), and flagellin equivalents (38-fold), all P<0.01. Analysis of representative strains of the major bacterial groups of the human intestine revealed that enterobacterial species are likely to be more significant contributors of soluble TLR2 and TLR4 stimulants to the intestinal milieu than Bacteroides species or Gram-positive Firmicutes.
  
  
  CONCLUSIONS
  We conclude that the induction of colitis or ileitis in mice is associated with significant disease-specific alterations to the PAMP profile of the gut microbiota.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom. ce55@le.ac.uk
authors.forename: Clett
authors.initials: C
authors.lastname: Erridge
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Duncan
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
mesh_terms: D000328:Adult; D000818:Animals; D001419:Bacteria / Q000276:immunology; D002460:Cell Line; D003092:Colitis / Q000209:etiology / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D005408:Flagellin / Q000378:metabolism*; D006801:Humans; D007079:Ileitis / Q000209:etiology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D055666:Lipopeptides / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism; D014123:Toxoplasmosis / Q000150:complications; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology; D055815:Young Adult
chemical_list: D055666:Lipopeptides; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D005408:Flagellin