Publication: Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
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Date
2016-07-01
Authors
Martín Sánchez, María Rosario Fátima ; Tyrkalska, Sylwia D. ; Candel Camacho, Sergio ; Angosto, Diego ; Gómez Abellán, Victoria ; García Moreno, Diana ; Zapata Pérez, Rubén ; Sánchez Ferrer, Álvaro ; Pelegrín Vivancos, Pablo ; Mulero Méndez, Victoriano Francisco ; Sepulcre Cortés, María Pilar
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/ncomms12077
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info:eu-repo/semantics/article
Description
Abstract
Inflammasomes are cytosolic molecular platforms that alert the immune system about thepresence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4),an IFNg-inducible GTPase protein harbouring a C-terminal CARD domain, is required for theinflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo.Despite the presence of the CARD domain, Gbp4 requires the universal inflammasomeadaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophilsare recruited to the infection site through the inflammasome-independent production of thechemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearancethrough the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our resultspoint to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis andbacterial clearance by neutrophils and suggest that transient activation of the inflammasomemay be used to treat bacterial infections.
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Citation
Nat Commun 7, 12077 (2016)
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