Transient activation of mucosal effector immune responses by resident intestinal bacteria in normal hosts is regulated by interleukin-10 signalling
Cong Wu
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
Search for more papers by this authorR. Balfour Sartor
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
Search for more papers by this authorCorresponding Author
Kehe Huang
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
Correspondence: Susan L. Tonkonogy, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. Email: [email protected] and Kehe Huang, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Email: [email protected]
Senior author: Susan L. Tonkonogy
Search for more papers by this authorCorresponding Author
Susan L. Tonkonogy
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
Correspondence: Susan L. Tonkonogy, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. Email: [email protected] and Kehe Huang, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Email: [email protected]
Senior author: Susan L. Tonkonogy
Search for more papers by this authorCong Wu
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
Search for more papers by this authorR. Balfour Sartor
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
Search for more papers by this authorCorresponding Author
Kehe Huang
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
Correspondence: Susan L. Tonkonogy, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. Email: [email protected] and Kehe Huang, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Email: [email protected]
Senior author: Susan L. Tonkonogy
Search for more papers by this authorCorresponding Author
Susan L. Tonkonogy
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
Correspondence: Susan L. Tonkonogy, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. Email: [email protected] and Kehe Huang, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Email: [email protected]
Senior author: Susan L. Tonkonogy
Search for more papers by this authorSummary
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.
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