title: Oral tolerance induced by enterobacteria altered the process of lymphocyte recruitment to intestinal microvessels: roles of endothelial cell adhesion molecules, TGF-beta and negative regulators of TLR signaling.
abstract: OBJECTIVE
  Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)-induced inflammatory conditions.
  
  
  METHODS
  Interaction of T-cells with ileal microvessels was monitored by using an intravital microscope in mice under germ-free (GF) and specific pathogen-free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection.
  
  
  RESULTS
  Adherence of T-cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T-cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T-cells in SPF mice. A significant induction of increase in mRNA expression of IRAK-M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF-beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment.
  
  
  CONCLUSIONS
  Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK-M and TGF-beta.
authors.affiliation: Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Okada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okudaira
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Matsunaga
authors.forename: Syunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nagao
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D002634:Chemotaxis, Leukocyte; D004727:Endothelium; D004755:Enterobacteriaceae / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology*; D007422:Intestines / Q000098:blood supply*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D055806:Microvessels / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D051193:Toll-Like Receptors; D015533:Transcriptional Activation / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
chemical_list: D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse