Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12077
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Funding
- Spanish Ministry of Economy and Competiveness [BIO2011-23400, BIO2014-52655-R, AGL2012-39674, BIO2013-45336-R]
- Fondos Europeos de Desarrollo Regional/European Regional Development Funds
- European 7th Framework Initial Training Network FishForPharma (PhD fellowship) [PITG-GA-2011-289209]
- Sara Borrell postdoc grant from the Instituto Salud Carlos III [CD12/00523]
- European Research Council [ERC-2013-CoG 614578]
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Inflammasomes are cytosolic molecular platforms that alert the immune system about the presence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4), an IFN gamma-inducible GTPase protein harbouring a C-terminal CARD domain, is required for the inflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo. Despite the presence of the CARD domain, Gbp4 requires the universal inflammasome adaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4 is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophils are recruited to the infection site through the inflammasome-independent production of the chemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearance through the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our results point to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis and bacterial clearance by neutrophils and suggest that transient activation of the inflammasome may be used to treat bacterial infections.
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