TOXOPLASMA GONDII-INDUCED IMMUNE SUPPRESSION BY HUMAN PERIPHERAL-BLOOD MONOCYTES - ROLE OF GAMMA-INTERFERON

The ability of Toxoplasma gondii to evade the host immune response dur ing primary infection in humans is poorly understood. In murine toxopl asmosis, infected spleen macrophages release soluble factors that medi ate a transient immunosuppression, which may allow the parasite to bec ome established. When an enriched population of human monocytes from s eronegative individuals was incubated with toxoplasmas in vitro, solub le factors that mediated marked suppression of mitogen-induced lymphoc yte DNA synthesis were released, Irradiated tachyzoites that do not un dergo replication were sufficient stimuli for near-maximal soluble fac tor release. Up to 50% of the soluble factor-mediated suppression is a ttributable to a gamma interferon (IFN-gamma)-dependent pathway, and t he mediator of the remaining inhibition is neither interleukin-10, tra nsforming growth factor beta, prostaglandin E(2), lipoxygenase product s, nitric oxide, nor tumor necrosis factor alpha-induced mitochondrial cell-derived reactive oxygen intermediates. IFN-gamma also mediates t he up-regulation of an antigen-presenting cell phenotype by both infec ted and uninfected macrophages. However, IFN-gamma does not activate m acrophages to become toxoplasmacidal; instead, intracellular toxoplasm as replicate and reinfect, eventually lysing the macrophage population . These results suggest that T. gondii is able to evade the naive host immune response by induction of soluble immunosuppressive factors tha t allow the parasite to become established during an acute infection.