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

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

doi:10.1016/j.immuni.2015.10.013

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

Anannya Bhattacharya
, Ahmed N. Hegazy
, Nikolaus Deigendesch
, Lindsay Kosack
, Jovana Cupovic
, Richard K. Kandasamy
, Andrea Hildebrandt
, Doron Merkler
, Anja A. Kühl
, Bojan Vilagos
, Christopher Schliehe
, Isabel Panse
, Kseniya Khamina
, Hatoon Baazim
, Isabelle Arnold
, Lukas Flatz
, Haifeng C. Xu
, Philipp A. Lang
, Alan Aderem
, Akinori Takaoka

Giulio Superti-Furga, Jacques Colinge, Burkhard Ludewig, Max Löhning, Andreas Bergthaler^*

^*Corresponding author for this work

Austrian Academy of Sciences
Charité – Universitätsmedizin Berlin
German Rheumatism Research Centre Berlin
University of Oxford
Max Planck Institute for Infection Biology
Cantonal Hospital St. Gallen
University of Geneva
University of Göttingen
Heinrich Heine University Düsseldorf
Seattle Biomedical Research Institute
Hokkaido University
Medical University of Vienna
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

Research output: Contribution to journal › Article › Academic › peer-review

56 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	974-986
Number of pages	13
Journal	Immunity
Volume	43
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2015.10.013
Publication status	Published - 17 Nov 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

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Bhattacharya, A., Hegazy, A. N., Deigendesch, N., Kosack, L., Cupovic, J., Kandasamy, R. K., Hildebrandt, A., Merkler, D., Kühl, A. A., Vilagos, B., Schliehe, C., Panse, I., Khamina, K., Baazim, H., Arnold, I., Flatz, L., Xu, H. C., Lang, P. A., Aderem, A., ... Bergthaler, A. (2015). Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity, 43(5), 974-986. https://doi.org/10.1016/j.immuni.2015.10.013

@article{0e91af2caba94d3bbc8e3fce0ae94be1,

title = "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.",

author = "Anannya Bhattacharya and Hegazy, \{Ahmed N.\} and Nikolaus Deigendesch and Lindsay Kosack and Jovana Cupovic and Kandasamy, \{Richard K.\} and Andrea Hildebrandt and Doron Merkler and K{\"u}hl, \{Anja A.\} and Bojan Vilagos and Christopher Schliehe and Isabel Panse and Kseniya Khamina and Hatoon Baazim and Isabelle Arnold and Lukas Flatz and Xu, \{Haifeng C.\} and Lang, \{Philipp A.\} and Alan Aderem and Akinori Takaoka and Giulio Superti-Furga and Jacques Colinge and Burkhard Ludewig and Max L{\"o}hning and Andreas Bergthaler",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = nov,

day = "17",

doi = "10.1016/j.immuni.2015.10.013",

language = "English",

volume = "43",

pages = "974--986",

journal = "Immunity",

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Bhattacharya, A, Hegazy, AN, Deigendesch, N, Kosack, L, Cupovic, J, Kandasamy, RK, Hildebrandt, A, Merkler, D, Kühl, AA, Vilagos, B, Schliehe, C, Panse, I, Khamina, K, Baazim, H, Arnold, I, Flatz, L, Xu, HC, Lang, PA, Aderem, A, Takaoka, A, Superti-Furga, G, Colinge, J, Ludewig, B, Löhning, M & Bergthaler, A 2015, 'Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage', Immunity, vol. 43, no. 5, pp. 974-986. https://doi.org/10.1016/j.immuni.2015.10.013

TY - JOUR

T1 - Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage

AU - Bhattacharya, Anannya

AU - Hegazy, Ahmed N.

AU - Deigendesch, Nikolaus

AU - Kosack, Lindsay

AU - Cupovic, Jovana

AU - Kandasamy, Richard K.

AU - Hildebrandt, Andrea

AU - Merkler, Doron

AU - Kühl, Anja A.

AU - Vilagos, Bojan

AU - Schliehe, Christopher

AU - Panse, Isabel

AU - Khamina, Kseniya

AU - Baazim, Hatoon

AU - Arnold, Isabelle

AU - Flatz, Lukas

AU - Xu, Haifeng C.

AU - Lang, Philipp A.

AU - Aderem, Alan

AU - Takaoka, Akinori

AU - Superti-Furga, Giulio

AU - Colinge, Jacques

AU - Ludewig, Burkhard

AU - Löhning, Max

AU - Bergthaler, Andreas

PY - 2015/11/17

Y1 - 2015/11/17

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84947424572

U2 - 10.1016/j.immuni.2015.10.013

DO - 10.1016/j.immuni.2015.10.013

M3 - Article

C2 - 26588782

AN - SCOPUS:84947424572

SN - 1074-7613

VL - 43

SP - 974

EP - 986

JO - Immunity

JF - Immunity

IS - 5

ER -

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

Abstract

Bibliographical note

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