Nitric oxide synthase in innate and adaptive immunity: an update

Trends Immunol. 2015 Mar;36(3):161-78. doi: 10.1016/ Epub 2015 Feb 13.


Thirty years after the discovery of its production by activated macrophages, our appreciation of the diverse roles of nitric oxide (NO) continues to grow. Recent findings have not only expanded our understanding of the mechanisms controlling the expression of NO synthases (NOS) in innate and adaptive immune cells, but have also revealed new functions and modes of action of NO in the control and escape of infectious pathogens, in T and B cell differentiation, and in tumor defense. I discuss these findings, in the context of a comprehensive overview of the various sources and multiple reaction partners of NO, and of the regulation of NOS2 by micromilieu factors, antisense RNAs, and 'unexpected' cytokines.

Keywords: B cells; NOS2/iNOS; NOS3/eNOS); Th17 cells; antimicrobial activity; microenvironment; myeloid cells; nitric oxide synthases (NOS1/nNOS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Bacteria / immunology
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate*
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / genetics
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / immunology
  • Isoenzymes / genetics
  • Isoenzymes / immunology
  • Lymphocytes / immunology
  • Macrophage Activation
  • Macrophages / immunology*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / immunology*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / immunology*
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology
  • Signal Transduction


  • IRF9 protein, human
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Isoenzymes
  • STAT Transcription Factors
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II