Induction and regulation of host cell-mediated immunity by Toxoplasma gondii.
Toxoplasma gondii is a highly infectious intracellular parasite which, if left unchecked by the immune system, rapidly overwhelms its intermediate hosts, as illustrated by the pathogenesis of toxoplasmic encephalitis in patients with AIDS. In order to insure both its host's and consequently its own survival simultaneously, T. gondii induces a potent gamma-interferon (IFN-gamma)-dependent cell-mediated immunity early in infection that controls the replication of the protozoan and facilitates transformation into the dormant cyst stage. The protective IFN-gamma is derived from three sources: natural killer cells; and CD4+ and CD8+ T lymphocytes, which can partially compensate for each other in knockout mice lacking the appropriate major histocompatibility complex-restricting elements. At least two properties of the parasite appear to be responsible for the early induction of these effector cells. The first is a hydrophobic molecule (or group of related molecules) that triggers interleukin 12 (IL-12), tumour necrosis factor alpha and IL-1beta synthesis in macrophages. This response can also promote HIV replication in the same cells. The second is a superantigen activity that drives IFN-gamma-producing Vbeta5+ CD8+ T cells. These potentially lethal responses are later regulated through the triggering of IL-10 and by the induction of anergy in the superantigen-stimulated Vbeta5+ T cell population.
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Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Denkers
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Gazzinelli
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D000818:Animals; D006678:HIV / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D015846:Monokines / Q000096:biosynthesis; D018089:Superantigens / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
D015846:Monokines; D018089:Superantigens; D007371:Interferon-gamma