Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice

Mégane Nascimento, Aurélie Gombault, Norinne Lacerda-Queiroz, Corinne Panek, Florence Savigny, Malak Sbeity, Manon Bourinet, Marc Le Bert , Nicolas Riteau, Bernhard Ryffel, Valérie F. J. Quesniaux & Isabelle Couillin


University of Orleans and CNRS, INEM-UMR7355, Orleans, France.


Correspondence and requests for materials should be addressed to I.C. (email:


Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.


Chronic obstructive pulmonary disease
Pattern recognition receptors
Published by

Scientific Reports