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

Benmerzoug, Sulayman; Rose, Stephanie; Bounab, Badreddine; Gosset, David; Duneau, Laure; Chenuet, Pauline; Mollet, Lucile; Le Bert, Marc; Lambers, Christopher; Geleff, Silvana; Roth, Michael; Fauconnier, Louis; Sedda, Delphine; Carvalho, Clarisse; Perche, Olivier; Laurenceau, David; Ryffel, Bernhard; Apetoh, Lionel; Kızıltunç, Ahmet; Uslu, Hakan; Albez, Fadime Sultan; Akgun, Metin; Togbe, Dieudonnee; Quesniaux, Valerie F. J.

doi:10.1038/s41467-018-07425-1

Makale Tam Makale Uluslararası 2018

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

Sulayman Benmerzoug, Stephanie Rose, Badreddine Bounab, David Gosset, Laure Duneau, Pauline Chenuet, Lucile Mollet, Marc Le Bert, Christopher Lambers, Silvana Geleff, Michael Roth, Louis Fauconnier, Delphine Sedda, Clarisse Carvalho, Olivier Perche, David Laurenceau, Bernhard Ryffel, Lionel Apetoh, Ahmet Kızıltunç, Hakan Uslu, Fadime Sultan Albez, Metin Akgun, Dieudonnee Togbe, Valerie F. J. Quesniaux

NATURE COMMUNICATIONS Cilt 9 · 06.12.2018

DOI ile aç

Özet

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.

Atıf için künye

Benmerzoug, S., Rose, S., Bounab, B., Gosset, D., Duneau, L., Chenuet, P., Mollet, L., Le Bert, M., Lambers, C., Geleff, S., Roth, M., Fauconnier, L., Sedda, D., Carvalho, C., Perche, O., Laurenceau, D., Ryffel, B., Apetoh, L., Kızıltunç, A., … Quesniaux, V. F. J. (2018). STING-dependent sensing of self-DNA drives silica-induced lung inflammation. NATURE COMMUNICATIONS, 9. https://doi.org/10.1038/s41467-018-07425-1

BibTeX

@article{benmerzoug2018-235227,
  author = {Benmerzoug, Sulayman and Rose, Stephanie and Bounab, Badreddine and Gosset, David and Duneau, Laure and Chenuet, Pauline and Mollet, Lucile and Le Bert, Marc and Lambers, Christopher and Geleff, Silvana and Roth, Michael and Fauconnier, Louis and Sedda, Delphine and Carvalho, Clarisse and Perche, Olivier and Laurenceau, David and Ryffel, Bernhard and Apetoh, Lionel and Kızıltunç, Ahmet and Uslu, Hakan and Albez, Fadime Sultan and Akgun, Metin and Togbe, Dieudonnee and Quesniaux, Valerie F. J.},
  title = {STING-dependent sensing of self-DNA drives silica-induced lung inflammation},
  journal = {NATURE COMMUNICATIONS},
  year = {2018},
  volume = {9},
  issn = {2041-1723},
  doi = {10.1038/s41467-018-07425-1},
  url = {https://akademik.atauni.edu.tr/yayinlar/235227-sting-dependent-sensing-of-self-dna-drives-silica-induced-lung-inflammation}
}