The apical complex of Toxoplasma gondii enables it to invade virtually all nucleated cells in warm-blooded animals, including humans, making it a parasite of global importance. Anti-T. gondii cellular defense mechanisms depend largely on interferon (IFN)-γ production by immune cells. However, the molecular mechanism of IFN-β-mediated defense remains largely unclear. Here, mouse peritoneal macrophages and murine embryonic fibroblasts (MEFs) primed with recombinant IFN-β and IFN-γ showed different pathways of activation. Treatment of these cells with IFN-β or IFN-γ inhibited T. gondii (Type II PLK strain) growth. Priming macrophages with IFN-β had no effect on inflammatory cytokine expression, inducible nitric oxide synthase or indoleamine 2,3-dioxygenase, nor did it have an effect on their metabolites, nitric oxide and kynurenine, respectively. In contrast, IFN-γ stimulation was characterized by classical macrophage activation and T. gondii elimination. IFN-β activation recruited the immunity-related GTPase M1 (IRGM1) to the parasitophorous vacuole in the macrophages and MEFs. Anti-toxoplasma activities induced by IFN-β were significantly reduced after IRGM1 knockdown in murine macrophages and in IRGM1 deficient MEFs. Thus, this study unravels an alternative pathway of macrophage activation by IFN-β and provides a mechanistic explanation for the contribution of IRGM1 induced by IFN-β to the elimination of T. gondii.
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