Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii

In vitro studies demonstrated that microglia and astrocytes produce IFN-gamma in response to various stimulations, including LPS. However, the physiological role of IFN-gamma production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-gamma production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-gamma production by brain-resident cells is essential for upregulating IFN-gamma-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-gamma only in CD11b(+) cells suggested that IFN-gamma production by microglia, which is the only CD11b(+) cell population among brainresident cells, is able to suppress the parasite growth. Furthermore, IFN-gamma produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-gamma produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii.