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Science 7 May 1999:
Vol. 284. no. 5416, pp. 951 - 955
DOI: 10.1126/science.284.5416.951
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Reports

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

Andreas Diefenbach, 1* Heike Schindler, 1 Martin Röllinghoff, 1 Wayne M. Yokoyama, 2 Christian Bogdan 1dagger

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-gamma (IFN-gamma ) 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-alpha /beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.

1 Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen, Wasserturmstrasse 3, D-91054 Erlangen, Germany.
2 Howard Hughes Medical Institute, Rheumatology Division Box 8045, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
*   Present address: Department of Molecular and Cell Biology and Cancer Research Laboratory, 485 LSA, University of California, Berkeley, CA 94720, USA.

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

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