Human microglial cell defense against Toxoplasma gondii. The role of cytokines

Abstract

Microglia may play an important role in host defense of the central nervous system against Toxoplasma gondii, and cytokines produced by these glial cells may participate in their antitoxoplasma activity. In our study, the antitoxoplasma activity of human fetal microglia was investigated. The RH strain of T. gondii multiplied readily in these glial cells. IFN-gamma/LPS-treated microglia limited (p < 0.01) T. gondii growth by reducing entry of this parasite rather than intracellular multiplication. More than 90% of the antitoxoplasma activity of activated microglia was blocked (p < 0.01) by neutralizing antibodies to TNF-alpha or IL-6 (but not to IL-1 or TGF-beta), suggesting that these proinflammatory cytokines play a role in the inhibitory process. Consistent with this hypothesis, treatment of microglia with TNF-alpha or IL-6 (in the presence or absence of IFN-gamma) inhibited (p < 0.01), in a dose-dependent manner, T. gondii growth. Inasmuch as NGMA did not affect cytokine-mediated antitoxoplasma activity of microglia, nitric oxide appears not to be involved in this host defense function of human fetal microglia. Results of our study suggest that the host defense activity of human microglia against T. gondii is dependent primarily on the activating properties of IFN-gamma, TNF-alpha, and IL-6.