6533b85afe1ef96bd12b8cce
RESEARCH PRODUCT
IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.
Nir YogevTegest AychekKi-wook KimDaniel J. CuaAri WaismanSimon YonaAlexander MildnerSteffen JungNardy LamplLouis BoonShlomit Reich-zeligersubject
ChemokineColonCX3C Chemokine Receptor 1General Physics and Astronomychemical and pharmacologic phenomenaMice TransgenicInterleukin-23General Biochemistry Genetics and Molecular BiologyMonocytesArticleMicrobiologyInterferon-gammaMiceIntestinal mucosaAntigens CDImmunopathologyCitrobacter rodentiummedicineAnimalsHomeostasisInterferon gammaIntestinal MucosaImmunity MucosalMultidisciplinaryCD11b AntigenbiologyInterleukinsMacrophagesEnterobacteriaceae InfectionsGeneral ChemistryMononuclear phagocyte systemDendritic CellsInterleukin-12Survival AnalysisImmunity InnateIntegrin alpha MGene Expression RegulationImmunologyInterleukin 12biology.proteinCitrobacter rodentiumTh17 CellsReceptors ChemokineIntegrin alpha Chainsmedicine.drugSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-10-02 | Nature communications |