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

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 IL-1β and IL-18. AIM2 is critical for host defense against DNA viruses and bacteria that replicate in the cytosol, such as Francisella novicida. AIM2 activation by F. novicida requires bacteriolysis, yet whether this process is accidental or a host-driven immune mechanism remained unclear. Using siRNA screening for nearly 500 interferon-stimulated genes, we identified guanylate-binding proteins GBP2 and GBP5 as key AIM2 activators during F. novicida infection. Their prominent role was validated in vitro and in a mouse model of tularemia. Mechanistically, these two GBPs target cytosolic F. novicida and promote bacteriolysis. Thus, besides their role in host defense against vacuolar pathogens, GBPs also facilitate the presentation of ligands by directly attacking cytosolic bacteria.
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https://hal.archives-ouvertes.fr/hal-01924091
Contributor : Laure-Hélène Davoine <>
Submitted on : Thursday, November 15, 2018 - 4:25:02 PM
Last modification on : Wednesday, December 18, 2019 - 1:48:11 AM

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Etienne Meunier, Pierre Wallet, Roland Dreier, Stéphanie Costanzo, Leonie Anton, et al.. Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nature Immunology, Nature Publishing Group, 2015, 16 (5), pp.476 - 484. ⟨10.1038/ni.3119⟩. ⟨hal-01924091⟩

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