Requirement for type 2 NO synthase for IL-12 signaling in innate immunity
A Diefenbach, H Schindler, M Rollinghoff… - Science, 1999 - science.org
A Diefenbach, H Schindler, M Rollinghoff, WM Yokoyama, C Bogdan
Science, 1999•science.orgInterleukin-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 Stat4 (the central
signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required …
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 Stat4 (the central
signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required …
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.
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