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IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
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IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
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Journal Article
IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
2015
Overview
Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX
3
CR1
+
mononuclear phagocytes are critical inducers of the innate response to
Citrobacter rodentium
infection. Specifically, the absence of IL-23 expression in macrophages or CD11b
+
DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103
+
CD11b
−
DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103
+
CD11b
−
DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103
−
CD11b
+
DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103
+
CD11b
−
DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology.
Macrophages and dendritic cells contribute to gut homeostasis and mucosal immune defense. Here, Aychek
et al
. describe an IL-23-based crosstalk between these cells that prevents lethal immunopathology during
Citrobacter rodentium
infection.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 13/21
/ 13/31
/ 64/60
/ Animals
/ Citrobacter rodentium - immunology
/ Citrobacter rodentium - pathogenicity
/ Dendritic Cells - immunology
/ Dendritic Cells - microbiology
/ Enterobacteriaceae Infections - immunology
/ Enterobacteriaceae Infections - microbiology
/ Enterobacteriaceae Infections - mortality
/ Enterobacteriaceae Infections - pathology
/ Humanities and Social Sciences
/ Integrin alpha Chains - genetics
/ Integrin alpha Chains - immunology
/ Interferon-gamma - immunology
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - microbiology
/ Intestinal Mucosa - pathology
/ Mice
/ Receptors, Chemokine - genetics
/ Receptors, Chemokine - immunology
/ Science
