Effects of cytokines on multiplication of Toxoplasma gondii in microglial cells

Chun C. Chao, Shuxian Hu, Genya Gekker, William J. Novick, Jack S. Remington, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Microglia may play a role in host defense against Toxoplasma gondii in the central nervous system. In our study, the antitoxoplasma activity of murine microglia was investigated. T. gondii multiplied readily in cultured microglial cells, and activation of these cells with IFN-γ plus LPS suppressed (p < 0.01) intracellular growth of this parasite. This antitoxoplasma defense of activated microglia was significantly blocked by neutralizing antibodies against TNF-α and transforming growth factor-β, suggesting that these cytokines play a role in the inhibitory process. Consistent with this hypothesis, activation of microglia with IFN-γ plus TNF-α or transforming growth factor-β inhibited, in a dose-dependent manner, T. gondii multiplication. Treatment with pentoxifylline or dexamethasone, drugs that suppress production of TNF-α, prevented (p < 0.01) the microglia from exerting an anti-T. gondii effect. These findings suggest that the host defense function of microglia against T. gondii is dependent primarily on the activating properties of IFN-γ and TNF-α, and that agents that interfere with cytokine-mediated activation may promote the pathogenesis of this infection.

Original languageEnglish (US)
Pages (from-to)3404-3410
Number of pages7
JournalJournal of Immunology
Volume150
Issue number8 I
StatePublished - 1993

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