Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage
Anannya Bhattacharya
,
Ahmed n. Hegazy
(1, 2, 3)
,
Nikolaus Deigendesch
(4)
,
Lindsay Kosack
,
Jovana Cupovic
(5)
,
Richard k. Kandasamy
,
Andrea Hildebrandt
,
Doron Merkler
(6)
,
Anja a. Kühl
(1)
,
Bojan Vilagos
,
Christopher Schliehe
,
Isabel Panse
(1)
,
Kseniya Khamina
,
Hatoon Baazim
,
Isabelle Arnold
(2)
,
Lukas Flatz
(5)
,
Haifeng c. Xu
(7)
,
Philipp a. Lang
(7)
,
Alan Aderem
,
Akinori Takaoka
(8)
,
Giulio Superti-Furga
(9)
,
Jacques Colinge
(10)
,
Burkhard Ludewig
(5)
,
Max Löhning
(1)
,
Andreas Bergthaler
1
Charité - UniversitätsMedizin = Berlin University Medicine
2 University of Oxford
3 DRFZ - Deutsches Rheuma-ForschungsZentrum
4 MPIIB - Max Planck Institute for Infection Biology
5 Brustzentrum Kantonsspital St. Gallen
6 UNIGE - Université de Genève = University of Geneva
7 Computer Science [Heinrich Heine University]
8 Hokkaido University [Sapporo, Japan]
9 Medizinische Universität Wien = Medical University of Vienna
10 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
2 University of Oxford
3 DRFZ - Deutsches Rheuma-ForschungsZentrum
4 MPIIB - Max Planck Institute for Infection Biology
5 Brustzentrum Kantonsspital St. Gallen
6 UNIGE - Université de Genève = University of Geneva
7 Computer Science [Heinrich Heine University]
8 Hokkaido University [Sapporo, Japan]
9 Medizinische Universität Wien = Medical University of Vienna
10 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
Anannya Bhattacharya
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Lindsay Kosack
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Richard k. Kandasamy
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Andrea Hildebrandt
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Bojan Vilagos
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Christopher Schliehe
- Fonction : Auteur
Kseniya Khamina
- Fonction : Auteur
Hatoon Baazim
- Fonction : Auteur
Alan Aderem
- Fonction : Auteur
Giulio Superti-Furga
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- PersonId : 915263
Jacques Colinge
- Fonction : Auteur
- PersonId : 184393
- IdHAL : jacques-colinge
- ORCID : 0000-0003-2466-4824
Andreas Bergthaler
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- PersonId : 1057080
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Résumé
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.