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.