AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

Di Micco, Antonia and Frera, Gianluca and Lugrin, Jérôme and Jamilloux, Yvan and Hsu, Erh-Ting and Tardivel, Aubry and De Gassart, Aude and Zaffalon, Léa and Bujisic, Bojan and Siegert, Stefanie and Quadroni, Manfredo and Broz, Petr and Henry, Thomas and Hrycyna, Christine A. and Martinon, Fabio. (2016) AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity. Proceedings of the National Academy of Sciences of the United States of America, 113 (32). E4671-E4680.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/43806/

Downloads: Statistics Overview


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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Infection Biology (Broz)
UniBasel Contributors:Broz, Petr
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Jan 2017 10:09
Deposited On:03 Jan 2017 10:09

Repository Staff Only: item control page