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

Bibliographic Details
Title:	Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida.
Authors:	Meunier, Etienne¹, Wallet, Pierre², Dreier, Roland F¹, Costanzo, Stéphanie², Anton, Leonie¹, Rühl, Sebastian¹, Dussurgey, Sébastien³, Dick, Mathias S¹, Kistner, Anne¹, Rigard, Mélanie², Degrandi, Daniel⁴, Pfeffer, Klaus⁴, Yamamoto, Masahiro⁵, Henry, Thomas², Broz, Petr¹
Source:	Nature Immunology. May2015, Vol. 16 Issue 5, p476-484. 9p. 8 Graphs.
Subject Terms:	FRANCISELLA novicida, GUANYLATE cyclase, CYTOSOL, CYTOKINES, DNA viruses, BACTERIOLYSIS
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. [ABSTRACT FROM AUTHOR]
	Copyright of Nature Immunology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database:	Academic Search Complete

More Details
ISSN:	15292908
DOI:	10.1038/ni.3119
Published in:	Nature Immunology
Language:	English