Significance Tuberculosis (TB) is an immunopathology, mostly of the lung, due to an overexuberant immune response to the bacterial pathogen Mycobacterium tuberculosis . Here, we demonstrate in vitro and in vivo that dendritic cell (DC) immunoreceptor (DCIR), a C-type lectin receptor expressed by DCs, modulates immunity to TB by sustaining type I IFN signaling in DCs. These findings were generalized beyond TB, in a model of in vivo antigen-presentation assay unrelated to M. tuberculosis , suggesting that they may extend to other pathologies, such as viral infections or autoimmune disorders. Thus, modulating DCIR activity may help to develop type I IFN-targeting therapies for a large repertoire of inflammatory disorders, including TB.