title: TLR signaling-induced CD103-expressing cells protect against intestinal inflammation.
abstract: BACKGROUND
  Toll-like receptor (TLR) expression in patients with inflammatory bowel disease is increased when compared with healthy controls. However, the impact of TLR signaling during inflammatory bowel disease is not fully understood.
  
  
  METHODS
  In this study, we used a murine model of acute phase inflammation in bone marrow chimeric mice to investigate in which cell type TLR2/4 signal induction is important in preventing intestinal inflammation and how intestinal dendritic cells are influenced. Mice were either fed with wild-type bacteria, able to initiate the TLR2/4 signaling cascade, or with mutant strains with impaired signal induction capacity.
  
  
  RESULTS
  The induction of the TLR2/4 signal cascade in epithelial cells resulted in inflammation in bone marrow chimeric mice, whereas induction in hematopoietic cells had an opposed function. Furthermore, feeding of wild-type bacteria prevented disease; however, differing signal induction of bacteria had no effect on lamina propria dendritic cell activation. In contrast, functional TLR2/4 signals resulted in increased frequencies of CD103-expressing lamina propria and mesenteric lymph node dendritic cells, which were able to ameliorate disease.
  
  
  CONCLUSIONS
  The TLR-mediated amelioration of disease, the increase in CD103-expressing cells, and the beneficial function of TLR signal induction in hematopoietic cells indicate that the increased expression of TLRs in patients with inflammatory bowel disease might result in counterregulation of the host and serve in preventing disease.
authors: *Interfacultary Institute for Microbiology and Infection Medicine, Department for Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; †Institute of Food Research, Norwich Research Park, Norwich, United Kingdom; ‡NIZO Food Research, Ede, the Netherlands; §TI Food and Nutrition, Wageningen, the Netherlands; ‖Host Microbe Interactomics Group, Wageningen University, Wageningen, the Netherlands; and ¶Institute of Pathology, University of Tübingen, Tübingen, Germany.
authors: Alexandra
authors: A
authors: Wittmann
authors: Peter A
authors: PA
authors: Bron
authors: Iris I
authors: II
authors: van Swam
authors: Michiel
authors: M
authors: Kleerebezem
authors: Patrick
authors: P
authors: Adam
authors: Kerstin
authors: K
authors: Gronbach
authors: Sarah
authors: S
authors: Menz
authors: Isabell
authors: I
authors: Flade
authors: Annika
authors: A
authors: Bender
authors: Andrea
authors: A
authors: Schäfer
authors: Ali Giray
authors: AG
authors: Korkmaz
authors: Raphael
authors: R
authors: Parusel
authors: Ingo B
authors: IB
authors: Autenrieth
authors: Julia-Stefanie
authors: JS
authors: Frick
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D004927:Escherichia coli Infections / Q000150:complications / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D039001:Integrin alpha Chains / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C091367:alpha E integrins; D016264:Dextran Sulfate