Cell-mediated immunity to Toxoplasma gondii: initiation, regulation and effector function.
Cell-mediated immune responses are essential for host control of intracellular infections. Toxoplasma gondii is a protozoan parasite that infects multiple vertebrate species and invades multiple cell types. Upon initial encounter with the immune system, the parasite rapidly induces production of the type-1 promoting cytokine IL-12 most likely from a subpopulation of dendritic cells. NK and T cells are then activated and triggered to synthesize IFN-gamma, the major mediator of host resistance during the acute and chronic phases of infection. During the acute phase, a concomitant IL-10 response dampens the systemic type-1 cytokine production and prevents lethal immunopathology. Cytokine (IFN-gamma und TNF-alpha) rather than cytotoxicity-based effector functions are more critical for protective immunity both during the acute and chronic phases of T. gondii infection. Both hemopoietic and non-hemopoietic cellular elements act as IFN-gamma and TNF-dependent effectors of host resistance. Type II iNOS-derived nitric oxide (NO) is required mainly for hemopoietic cell-derived effector cell activity in the central nervous system (CNS) during the chronic phase of infection. Nevertheless, in both the acute and chronic stages, IFN-gamma-dependent but iNOS-independent mechanism(s) play a major function in parasite control and their identification remains an important challenge for this field.
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Immunobiology Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D013601:T-Lymphocytes / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II