Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage

Immunity. 2015 Nov 17;43(5):974-86. doi: 10.1016/j.immuni.2015.10.013.


Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(-/-) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(-/-) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Hepatitis, Viral, Animal / immunology
  • Hepatocytes / immunology*
  • Immunity, Innate / immunology
  • Inflammation / immunology
  • Interferon Type I / immunology*
  • Killer Cells, Natural / immunology
  • Liver / immunology
  • Mice
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Oxidative Stress / immunology*
  • Signal Transduction / immunology
  • Superoxide Dismutase / immunology*
  • Superoxide Dismutase-1
  • T-Lymphocytes / immunology
  • Transcription, Genetic / immunology


  • Antioxidants
  • Interferon Type I
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1