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Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida

Meunier, Etienne and Wallet, Pierre and Dreier, Roland F. and Costanzo, Stéphanie and Anton, Leonie and Rühl, Sebastian and Dussurgey, Sébastien and Dick, Mathias S. and Kistner, Anne and Rigard, Mélanie and Degrandi, Daniel and Pfeffer, Klaus and Yamamoto, Masahiro and Henry, Thomas and Broz, Petr. (2015) Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nature immunology, Vol. 16, H. 5. pp. 476-484.

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Official URL: http://edoc.unibas.ch/dok/A6357894

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Abstract

The AIM2 inflammasome detects double-stranded DNA in the cytosol and induces caspase-1-dependent pyroptosis as well as release of the inflammatory cytokines interleukin 1β (IL-1β) and IL-18. AIM2 is critical for host defense against DNA viruses and bacteria that replicate in the cytosol, such as Francisella tularensis subspecies novicida (F. novicida). The activation of AIM2 by F. novicida requires bacteriolysis, yet whether this process is accidental or is a host-driven immunological mechanism has remained unclear. By screening nearly 500 interferon-stimulated genes (ISGs) through the use of small interfering RNA (siRNA), we identified guanylate-binding proteins GBP2 and GBP5 as key activators of AIM2 during infection with F. novicida. We confirmed their prominent role in vitro and in a mouse model of tularemia. Mechanistically, these two GBPs targeted cytosolic F. novicida and promoted bacteriolysis. Thus, in addition to their role in host defense against vacuolar pathogens, GBPs also facilitate the presentation of ligands by directly attacking cytosolic bacteria.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Infection Biology (Broz)
UniBasel Contributors:Broz, Petr and Meunier, Etienne and Dreier, Roland and Rühl, Sebastian and Dick, Mathias S.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature America
ISSN:1529-2908
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Jun 2015 08:52
Deposited On:05 Jun 2015 08:52

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