IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology

Nature Communications
Tegest AychekSteffen Jung

Abstract

Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) 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.

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Citations

Jul 25, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Hayley L EamesIrina A Udalova
Jun 18, 2015·Frontiers in Immunology·Mor GrossSteffen Jung
Jun 21, 2016·Immunological Reviews·Nicholas J Bessman, Gregory F Sonnenberg
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Oct 10, 2021·Proceedings of the National Academy of Sciences of the United States of America·Hong Bing YuKevan Jacobson

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
reverse
fluorescence-activated cell sorting
reverse transcription PCR
PMA
PCR
biopsies
biopsy
ELISA

Software Mentioned

Manager
GraphPad Prism
DP

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