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

Author

Listed:
  • Sulayman Benmerzoug

    (CNRS, UMR7355
    University of Orleans)

  • Stéphanie Rose

    (CNRS, UMR7355
    University of Orleans)

  • Badreddine Bounab

    (CNRS, UMR7355
    University of Orleans)

  • David Gosset

    (Center for Molecular Biophysics, CNRS UPR4301)

  • Laure Duneau

    (CNRS, UMR7355
    University of Orleans)

  • Pauline Chenuet

    (Artimmune SAS, rue Buffon)

  • Lucile Mollet

    (Center for Molecular Biophysics, CNRS UPR4301)

  • Marc Bert

    (CNRS, UMR7355
    University of Orleans)

  • 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
    University of Orleans)

  • Clarisse Carvalho

    (CNRS, UMR7355
    University of Orleans)

  • Olivier Perche

    (CNRS, UMR7355
    University of Orleans
    Regional Hospital Orleans)

  • David Laurenceau

    (CNRS, UMR7355
    University of Orleans
    Regional Hospital Orleans)

  • Bernhard Ryffel

    (CNRS, UMR7355
    University of Orleans)

  • 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
    University of Orleans)

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.

Suggested Citation

  • Sulayman Benmerzoug & Stéphanie Rose & Badreddine Bounab & David Gosset & Laure Duneau & Pauline Chenuet & Lucile Mollet & Marc Bert & Christopher Lambers & Silvana Geleff & Michael Roth & Louis Fauco, 2018. "STING-dependent sensing of self-DNA drives silica-induced lung inflammation," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07425-1
    DOI: 10.1038/s41467-018-07425-1
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