Microglia produce IFN-γ independently from T cells during acute toxoplasmosis in the brain

We previously reported a requirement of interferon-gamma (IFN-gamma) production by both T cells and cells other than T or natural killer (NK) cells in the brain for prevention of toxoplasmic encephalitis. In the present study, we examined whether microglia, the resident macrophage system in the brain, produce IFN-gamma in response to infection with Toxoplasma gondii in SCID and wild-type BALB/c mice. IFN-gamma was detected in the culture supernatants of microglia purified from the brains of SCID mice that had developed toxoplasmic encephalitis due to reactivation of infection. A significant increase in numbers of IFN-gamma-expressing microglia was also observed by immunostaining for this cytokine in the brains of SCID and BALB/c mice during the acute stage of acquired infection, and those numbers decreased in the later stage of infection in the BALB/c animals. These results indicate that microglia produce IFN-gamma in the presence and absence of T cells in response to reactivated or acute acquired infection in the brain. Because IFN-gamma is the essential effector molecule to control tachyzoites and because this cytokine is a potent inducer of expression of chemokines and MHC antigens important for recruitment and activation of T cells, IFN-gamma production by microglia might play a critical role in the early stage of tachyzoite proliferation in the brain by limiting parasite growth and initiating subsequent T cell immunity.