Requirement for type 2 NO synthase for IL-12 signaling in innate immunity

Andreas Diefenbach, Heike Schindler, Martin Röllinghoff, Wayne M. Yokoyama, Christian Bogdan

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

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 of Leishmania 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 State (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.

Original languageEnglish
Pages (from-to)951-955
Number of pages5
JournalScience
Volume284
Issue number5416
DOIs
StatePublished - May 7 1999

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