title: IL-10-producing intestinal macrophages prevent excessive antibacterial innate immunity by limiting IL-23 synthesis.
abstract: Innate immune responses are regulated in the intestine to prevent excessive inflammation. Here we show that a subset of mouse colonic macrophages constitutively produce the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, these macrophages are required to prevent intestinal pathology. IL-23 is significantly increased in infected mice with a myeloid cell-specific deletion of IL-10, and the addition of IL-10 reduces IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 leads to reduced mortality in the context of macrophage IL-10 deficiency. Transcriptome and other analyses indicate that IL-10-expressing macrophages receive an autocrine IL-10 signal. Interestingly, only transfer of the IL-10 positive macrophages could rescue IL-10-deficient infected mice. Therefore, these data indicate a pivotal role for intestinal macrophages that constitutively produce IL-10, in controlling excessive innate immune activation and preventing tissue damage after an acute bacterial infection.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Krause
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Venetia
authors.initials: V
authors.lastname: Morris
authors.affiliation: Bioinformatics Core Facility, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Greenbaum
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Park
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Unni
authors.initials: U
authors.lastname: Bjoerheden
authors.affiliation: Microscopy Core Facility, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Zbigniew
authors.identifier: 0000000219189216
authors.initials: Z
authors.lastname: Mikulski
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Muffley
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Jr-Wen
authors.initials: JW
authors.lastname: Shui
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Gisen
authors.initials: G
authors.lastname: Kim
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Yun-Cai
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Bjoern
authors.identifier: 0000000284576693
authors.initials: B
authors.lastname: Peters
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Masako
authors.identifier: 0000000254450846
authors.initials: M
authors.lastname: Murai
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009997:Osmotic Pressure; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity; D013312:Stress, Physiological; D058504:Th17 Cells
chemical_list: C556062:IL10 protein, mouse; D053583:Interleukin-1beta; D053759:Interleukin-23; D017673:Sodium Chloride, Dietary; D016753:Interleukin-10; D020170:Caspase 1