AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

作者：Di Micco Antonia; Frera Gianluca; Lugrin Jerome; Jamilloux Yvan; Hsu Erh Ting; Tardivel Aubry; De Gassart Aude; Zaffalon Lea; Bujisic Bojan; Siegert Stefanie; Quadroni Manfredo; Broz Petr; Henry Thomas; Hrycyna Christine A; Martinon Fabio^*

来源：Proceedings of the National Academy of Sciences, 2016, 113(32): E4671-E4680.

DOI：10.1073/pnas.1602419113

• inflammasome
• nuclear envelope stress
• DNA sensors
• zmpste24
• Nelfinavir

Inflammasomes are critical sensors that convey cellular stress and pathogen presence to the immune system by activating inflammatory caspases and cytokines such as IL-1 beta. 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.

• 出版日期2016-8-9