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

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.
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https://hal.umontpellier.fr/hal-02336008
Contributeur : Amandine Michel-Avella <>
Soumis le : lundi 28 octobre 2019 - 15:52:13
Dernière modification le : mardi 29 octobre 2019 - 01:38:42

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Anannya Bhattacharya, Ahmed n. Hegazy, Nikolaus Deigendesch, Lindsay Kosack, Jovana Cupovic, et al.. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity, Elsevier, 2015, 43 (5), pp.974-986. ⟨10.1016/j.immuni.2015.10.013⟩. ⟨hal-02336008⟩

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