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Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity

Science  07 May 1999:
Vol. 284, Issue 5416, pp. 951-955
DOI: 10.1126/science.284.5416.951

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Abstract

Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading ofLeishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-γ (IFN-γ) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.

  • * Present address: Department of Molecular and Cell Biology and Cancer Research Laboratory, 485 LSA, University of California, Berkeley, CA 94720, USA.

  • To whom correspondence should be addressed. E-mail: christian.bogdan{at}mikrobio.med.uni-erlangen.de

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