期刊
IMMUNITY
卷 43, 期 5, 页码 974-986出版社
CELL PRESS
DOI: 10.1016/j.immuni.2015.10.013
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资金
- DOC fellowships of the Austrian Academy of Sciences
- European Molecular Biology Organization (EMBO) long-term fellowship [ALTF 116-2012, ALTF 314-2012]
- German Academic Exchange Service (DAAD)
- Swiss National Science Foundation [PP00P3_152928]
- Klaus-Tschira Foundation
- Gebert-Ruf Foundation
- DAAD
- Alexander von Humboldt Foundation (SKA)
- German Research Council [SFB974, LA2558/5-1]
- ERC
- German Federal Ministry of Education and Research (BMBF, T-Sys)
- German Research Foundation [SFB618, TPC3, SFB650, TP28, LO1542/3-1]
- Volkswagen Foundation
- Austrian Academy of Sciences
- Austrian Science Foundation (FWF) [23991]
- Grants-in-Aid for Scientific Research [25253030] Funding Source: KAKEN
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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