title: Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice.
abstract: OBJECTIVE
  The intestinal microbiota is an important determinant of the mucosal response. In patients with inflammatory bowel diseases, the mucosal immune system has inappropriate interactions with the intestinal microbiota. We investigated how the composition of the intestinal microbiota affects its endotoxicity and development of colitis in mice.
  
  
  METHODS
  Germ-free C57BL/6J-Rag(1tm1Mom) (Rag1(-/-)) mice were colonized with 2 different types of complex intestinal microbiota. Colitis was induced in Rag1(-/-) mice by transfer of CD4(+)CD62L(+) T cells from C57BL/6J mice. Colonic tissues were collected and used for histologic analysis and cell isolation. Activation of lamina propria dendritic cells and T cells was analyzed by flow cytometry.
  
  
  RESULTS
  After transfer of CD4(+)CD62L(+) T cells, mice with intestinal Endo(lo) microbiota (a low proportion of Enterobacteriaceae, high proportion of Bacteroidetes, and low endotoxicity) maintained mucosal immune homeostasis, and mice with highly endotoxic Endo(hi) microbiota (a high proportion of Enterobacteriaceae and low proportion of Bacteroidetes) developed colitis. To determine whether the effects of Endo(hi) microbiota were related to the higher endotoxic activity of lipopolysaccharide (LPS), we compared LPS from Enterobacteriaceae with that of Bacteroidetes. Administration of Escherichia coli JM83 (wild-type LPS) to the mice exacerbated colitis, and Escherichia coli JM83 + htrBPG (mutated LPS, with lower endotoxicity, similar to that of Bacteroidetes) prevented development of colitis after transfer of the T cells to mice.
  
  
  CONCLUSIONS
  The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis after transfer of CD4(+)CD62L(+) T cells. This finding might aid the design of novel biologics or probiotics to treat inflammatory bowel disease.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gronbach
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Flade
authors.affiliation: Division of Structural Biochemistry, Research Center Borstel, Airway Research Center North (ARCN) and German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Holst
authors.affiliation: Division of Immunochemistry, Research Center Borstel, Airway Research Center North (ARCN) and German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.affiliation: Algorithms in Bioinformatics, ZBIT Center for Bioinformatics, University of Tübingen, Tübingen, Germany.
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Ruscheweyh
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wittmann
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Menz
authors.affiliation: Institute of Microoecology, Herborn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwiertz
authors.affiliation: Institute of Pathology, University of Tübingen, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Adam
authors.affiliation: German Centre for Infection Research (DZIF), Germany; Max von Pettenkofer-Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
authors.affiliation: German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Josenhans
authors.affiliation: German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.affiliation: Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Institute for Microbiology, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.affiliation: Algorithms in Bioinformatics, ZBIT Center for Bioinformatics, University of Tübingen, Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huson
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Germany. Electronic address: julia-stefanie.frick@med.uni-tuebingen.de.
authors.forename: Julia-Stefanie
authors.initials: JS
authors.lastname: Frick
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000302:isolation & purification; D005260:Female; D006487:Hemostasis / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007109:Immunity / Q000502:physiology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C064658:RAG-1 protein
keywords: Bacteria; IBD; Mouse Model; Prevention