2016 journal article

Transient activation of mucosal effector immune responses by resident intestinal bacteria in normal hosts is regulated by interleukin-10 signalling

IMMUNOLOGY, 148(3), 304–314.

author keywords: germ-free mice; interleukin-10; resident bacteria
MeSH headings : Animals; Antigens, Bacterial / immunology; B-Lymphocytes / immunology; Cells, Cultured; Colitis / etiology; Colitis / immunology; Disease Models, Animal; Escherichia coli / immunology; Escherichia coli Infections / complications; Escherichia coli Infections / immunology; Immunity, Mucosal; Interferon-gamma / metabolism; Interleukin-10 / genetics; Interleukin-10 / metabolism; Intestines / immunology; Intestines / microbiology; Lymphocyte Activation; Mice; Mice, 129 Strain; Mice, Knockout; Signal Transduction; Th1 Cells / immunology
Source: Web Of Science
Added: August 6, 2018

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.