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

Publication

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

Journal Paper/Review - Nov 17, 2015

Bhattacharya Anannya, Arnold Isabelle, Flatz Lukas, Xu Haifeng C, Lang Philipp A, Aderem Alan, Takaoka Akinori, Superti-Furga Giulio, Colinge Jacques, Ludewig Burkhard, Löhning Max, Baazim Hatoon, Khamina Kseniya, Panse Isabel, Hegazy Ahmed N, Deigendesch Nikolaus, Kosack Lindsay, Cupovic Jovana, Kandasamy Richard K, Hildebrandt Andrea, Merkler Doron, Kühl Anja A, Vilagos Bojan, Schliehe Christopher, Bergthaler Andreas

Citation

Bhattacharya A, Arnold I, Flatz L, Xu H, Lang P, Aderem A, Takaoka A, Superti-Furga G, Colinge J, Ludewig B, Löhning M, Baazim H, Khamina K, Panse I, Hegazy A, Deigendesch N, Kosack L, Cupovic J, Kandasamy R, Hildebrandt A, Merkler D, Kühl A, Vilagos B, Schliehe C, Bergthaler A. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity 2015; 43:974-86.

Type

Journal Paper/Review (English)

Journal

Immunity 2015; 43

Publication Date

Nov 17, 2015

Issn Electronic

1097-4180

Pages

974-86

Brief description/objective

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.