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

Bhattacharya, Anannya
Hegazy, Ahmed N
Deigendesch, Nikolaus
Kosack, Lindsay
Cupovic, Jovana
Kandasamy, Richard K
Hildebrandt, Andrea
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Published in Immunity. 2015, vol. 43, no. 5, p. 974-986
Abstract 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.
PMID: 26588782
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Research group La Sclérose en plaques (908)
Project FNS: PP00P3_152928
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BHATTACHARYA, Anannya et al. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. In: Immunity, 2015, vol. 43, n° 5, p. 974-986. doi: 10.1016/j.immuni.2015.10.013 https://archive-ouverte.unige.ch/unige:79114

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Deposited on : 2016-01-12

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