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 during primary infection in humans is poorly understood. In murine toxoplasmosis, infected spleen macrophages release soluble factors that mediate a transient immunosuppression, which may allow the parasite to become established. When an enriched population of human monocytes from seronegative individuals was incubated with toxoplasmas in vitro, soluble factors that mediated market suppression of mitogen-induced lymphocyte DNA synthesis were released. Irradiated tachyzoites that do not undergo replication were sufficient stimuli for near-maximal soluble factor release. Up to 50% of the soluble factor-mediated suppression is attributable to a gamma interferon (IFN-gamma)-dependent pathway, and the mediator of the remaining inhibition is neither interleukin-10, transforming growth factor beta, prostaglandin E2, lipoxygenase products, nitric oxide, nor tumor necrosis factor alpha-induced mitochondrial cell-derived reactive oxygen intermediates. IFN-gamma also mediates the up-regulation of an antigen-presenting cell phenotype by both infected and uninfected macrophages. However, IFN-gamma does not activate macrophages to become toxoplasmacidal; instead, intracellular toxoplasmas 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 that allow the parasite to become established during an acute infection.
Channon
J Y
JY
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Kasper
L H
LH
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology; D013491:Suppressor Factors, Immunologic / Q000502:physiology*; D014123:Toxoplasmosis / Q000276:immunology*
D011956:Receptors, Cell Surface; D013491:Suppressor Factors, Immunologic; D016753:Interleukin-10; D007371:Interferon-gamma; D015232:Dinoprostone