IFN-γ produced by brain-resident cells is crucial to control cerebral infection with Toxoplasma gondii

Abstract

Abstract In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations including LPS, a component of the outer membrane of Gram-negative bacteria. However, the physiological role of IFN-γ production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii, an obligate intracellular protozoan parasite, using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b+ cells suggested that IFN-γ production by microglia, which is the only CD11b+ cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ production by brain-resident cells is pivotal for upregulating cerebral expression of CXCL9 and CXCL10 chemokines and recruiting T cells into the brain to control the infection. These results indicate that IFN-γ 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.