The role of nitric oxide in innate immunity

Immunol Rev. 2000 Feb;173:17-26. doi: 10.1034/j.1600-065x.2000.917307.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Killer Cells, Natural
  • Leishmaniasis, Cutaneous / immunology*
  • Mice
  • Models, Immunological
  • Nitric Oxide / immunology*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II


  • Cytokines
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse