title: Transient activation of mucosal effector immune responses by resident intestinal bacteria in normal hosts is regulated by interleukin-10 signalling.
abstract: Interleukin-10 (IL-10) is a key regulator of mucosal homeostasis. In the current study we investigated the early events after monoassociating germ-free (GF) wild-type (WT) mice with an Escherichia coli strain that we isolated previously from the caecal contents of a normal mouse housed under specific pathogen-free conditions. Our results show that interferon-γ (IFN-γ) secreted by mesenteric lymph node (MLN) cells from both IL-10 deficient mice and WT mice, stimulated ex vivo with E. coli lysate, was dramatically higher at day 4 after monoassociation compared with IFN-γ secreted by cells from GF mice without E. coli colonization. Production of IFN-γ rapidly and progressively declined after colonization of WT but not IL-10-deficient mice. The E. coli lysate-stimulated WT MLN cells also produced IL-10 that peaked at day 4 and subsequently declined, but not as precipitously as IFN-γ. WT cells that express CD4, CD8 and NKp46 produced IFN-γ; WT CD4-positive cells and B cells produced IL-10. Recombinant IL-10 added to E. coli-stimulated MLN cell cultures inhibited IFN-γ secretion in a dose-dependent fashion. MLN cells from WT mice treated in vivo with neutralizing anti-IL-10 receptor antibody produced more IFN-γ compared with MLN cells from isotype control antibody-treated mice. These findings show that a resident E. coli that induces chronic colitis in monoassociated IL-10-deficient mice rapidly but transiently activates the effector immune system in normal hosts, in parallel with induction of protective IL-10 produced by B cells and CD4(+) cells that subsequently suppresses this response to mediate mucosal homeostasis.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.|Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Kehe
authors.initials: K
authors.lastname: Huang
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tonkonogy
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology*; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008213:Lymphocyte Activation; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: germ-free mice; interleukin-10; resident bacteria