ABSTRACTThe cytokine gamma interferon (IFN-γ) is critical for resistance toToxoplasma gondii. IFN-γ strongly activates macrophages and nonphagocytic host cells to limit intracellular growth ofT. gondii; however, the cellular factors that are required for this effect are largely unknown. We have shown previously that IGTP and LRG-47, members of the IFN-γ-regulated family of p47 GTPases, are required for resistance to acuteT. gondiiinfections in vivo. In contrast, IRG-47, another member of this family, is not required. In the present work, we addressed whether these GTPases are required for IFN-γ-induced suppression ofT. gondiigrowth in macrophages in vitro. Bone marrow macrophages that lacked IGTP or LRG-47 displayed greatly attenuated IFN-γ-induced inhibition ofT. gondiigrowth, while macrophages that lacked IRG-47 displayed normal inhibition. Thus, the ability of the p47 GTPases to limit acute infection in vivo correlated with their ability to suppress intracellular growth in macrophages in vitro. Using confocal microscopy and sucrose density fractionation, we demonstrated that IGTP largely colocalizes with endoplasmic reticulum markers, while LRG-47 was mainly restricted to the Golgi. Although both IGTP and LRG-47 localized to vacuoles containing latex beads, neither protein localized to vacuoles containing liveT. gondii. These results suggest that IGTP and LRG-47 are able to regulate host resistance to acuteT. gondiiinfections through their ability to inhibit parasite growth within the macrophage.