The role of nitric oxide in innate immunity.
Type 2 nitric oxide synthase (iNOS or NOS2) was originally described as an enzyme that is expressed in activated macrophages, generates nitric oxide (NO) from the amino acid L-arginine, and thereby contributes to the control of replication or killing of intracellular microbial pathogens. Since interferon (IFN)-gamma is the key cytokine for the induction of NOS2 in macrophages and the prototypic product of type 1 T-helper cells, high-level expression of NOS2 has been regarded to be mostly restricted to the adaptive phase of the immune response. In this review, we summarize data that demonstrate a prominent role of NOS2/NO also during innate immunity. During the early phase of infection with the intracellular pathogen Leishmania major, focally expressed NOS2/NO not only exerts antimicrobial activities but also controls the function of natural killer cells and the expression of cytokines such as IFN-gamma or transforming growth factor-beta. Some of these effects result from the function of NOS2/NO as an indispensable co-factor for the activation of Tyk2 kinase and, thus, for interleukin-12 and IFN-alpha/beta signaling in natural killer cells.
Bogdan
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Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, Germany. christian.bogdan@mikrobio.med.uni-erlangen.de
Röllinghoff
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Diefenbach
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D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D009569:Nitric Oxide / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
D016207:Cytokines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse