AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2016

AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

Aude de Gassart

Résumé

Inflammasomes are critical sensors that convey cellular stress and pathogen presence to the immune system by activating inflammatory caspases and cytokines such as IL-1β. The nature of endogenous stress signals that activate inflammasomes remains unclear. Here we show that an inhibitor of the HIV aspartyl protease, Nelfinavir, triggers inflammasome formation and elicits an IL-1R-dependent inflammation in mice. We found that Nelfinavir impaired the maturation of lamin A, a structural component of the nuclear envelope, thereby promoting the release of DNA in the cytosol. Moreover, deficiency of the cytosolic DNA-sensor AIM2 impaired Nelfinavir-mediated inflammasome activation. These findings identify a pharmacologic activator of inflammasome and demonstrate the role of AIM2 in detecting endogenous DNA release upon perturbation of nuclear envelope integrity.

Dates et versions

hal-01908865 , version 1 (30-10-2018)

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Citer

Antonia Di Micco, Gianluca Frera, Jérôme Lugrin, Yvan Jamilloux, Erh-Ting Hsu, et al.. AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113 (32), pp.E4671-4680. ⟨10.1073/pnas.1602419113⟩. ⟨hal-01908865⟩
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