STING-dependent sensing of self-DNA drives silica-induced lung inflammation

Sulayman Benmerzoug, Stéphanie Rose, Badreddine Bounab, David Gosset, Laure Duneau, Pauline Chenuet, Lucile Mollet, Marc Bert, Christopher Lambers, Silvana Geleff, Michael Roth, Louis Fauconnier, Delphine Sedda, Clarisse Carvalho, Olivier Perche, David Laurenceau, Bernhard Ryffel, Lionel Apetoh, Ahmet Kiziltunc, Hakan Uslu, Fadime Sultan Albez, Metin Akgun, Dieudonnée Togbe and Valerie F. J. Quesniaux ()
Additional contact information
Sulayman Benmerzoug: CNRS, UMR7355
Stéphanie Rose: CNRS, UMR7355
Badreddine Bounab: CNRS, UMR7355
David Gosset: Center for Molecular Biophysics, CNRS UPR4301
Laure Duneau: CNRS, UMR7355
Pauline Chenuet: Artimmune SAS, rue Buffon
Lucile Mollet: Center for Molecular Biophysics, CNRS UPR4301
Marc Bert: CNRS, UMR7355
Christopher Lambers: Lung Transplantation Program
Silvana Geleff: Medical University of Vienna
Michael Roth: University& University Hospital Basel
Louis Fauconnier: Artimmune SAS, rue Buffon
Delphine Sedda: CNRS, UMR7355
Clarisse Carvalho: CNRS, UMR7355
Olivier Perche: CNRS, UMR7355
David Laurenceau: CNRS, UMR7355
Bernhard Ryffel: CNRS, UMR7355
Lionel Apetoh: INSERM, U1231
Ahmet Kiziltunc: Atatürk University School of Medicine
Hakan Uslu: Atatürk University School of Medicine
Fadime Sultan Albez: Atatürk University School of Medicine
Metin Akgun: Atatürk University School of Medicine
Dieudonnée Togbe: Artimmune SAS, rue Buffon
Valerie F. J. Quesniaux: CNRS, UMR7355

Nature Communications, 2018, vol. 9, issue 1, 1-19

Abstract: Abstract Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway. Degradation of extracellular self-dsDNA by DNase I inhibits silica-induced STING activation and the downstream type I IFN response. Patients with silicosis have increased circulating dsDNA and CXCL10 in sputum, and patients with fibrotic interstitial lung disease display STING activation and CXCL10 in the lung. In vitro, while mitochondrial dsDNA is sensed by cGAS-STING in dendritic cells, in macrophages extracellular dsDNA activates STING independent of cGAS after silica exposure. These results reveal an essential function of STING-mediated self-dsDNA sensing after silica exposure, and identify DNase I as a potential therapy for silica-induced lung inflammation.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07425-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07425-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07425-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().