Toxoplasma gondii inhibits MHC class II expression in neural antigen-presenting cells by down-regulating the class II transactivator CIITA

Abstract

Major histocompatibility complex (MHC) class II expression by microglia and astrocytes is critical for CD4+-mediated immune responses within the central nervous system. Here, we demonstrate that the obligate intracellular parasite, Toxoplasma gondii, down-regulates activation-induced MHC class II expression in human-derived glioblastoma cells as well as in primary astrocytes and microglia from cortices of rat fetuses. Down-regulation of MHC class II proteins was predominantly observed in parasite-positive, but not parasite-negative, host cells of T. gondii-infected cell cultures. MHC class II transcript levels induced by IFN-gamma alone or in combination with TNF-alpha were also clearly diminished after parasitic infection. Furthermore, T. gondii dose-dependently down-regulated the transcript levels of the class II transactivator CIITA. These results suggest that T. gondii partially evade CD4+-mediated intracerebral immune responses, a mechanism which may contribute to long-term persistence of the parasite within the CNS.