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Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins

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  • Sylwia D. Tyrkalska

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca
    Instituto de Investigaciones Marinas, CSIC)

  • Sergio Candel

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Diego Angosto

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Victoria Gómez-Abellán

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Fátima Martín-Sánchez

    (Unidad de inflamación y Cirugía Experimental, CIBERehd, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca)

  • Diana García-Moreno

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Rubén Zapata-Pérez

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Álvaro Sánchez-Ferrer

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • María P. Sepulcre

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

  • Pablo Pelegrín

    (Unidad de inflamación y Cirugía Experimental, CIBERehd, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca)

  • Victoriano Mulero

    (Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca)

Abstract

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 IFNγ-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.

Suggested Citation

  • Sylwia D. Tyrkalska & Sergio Candel & Diego Angosto & Victoria Gómez-Abellán & Fátima Martín-Sánchez & Diana García-Moreno & Rubén Zapata-Pérez & Álvaro Sánchez-Ferrer & María P. Sepulcre & Pablo Pele, 2016. "Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins," Nature Communications, Nature, vol. 7(1), pages 1-17, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12077
    DOI: 10.1038/ncomms12077
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    Cited by:

    1. Rong Sun & Mingzhu Liu & Jianping Lu & Binbin Chu & Yunmin Yang & Bin Song & Houyu Wang & Yao He, 2022. "Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Vincenzo Torraca & Myrsini Kaforou & Jayne Watson & Gina M Duggan & Hazel Guerrero-Gutierrez & Sina Krokowski & Michael Hollinshead & Thomas B Clarke & Rafal J Mostowy & Gillian S Tomlinson & Vanessa , 2019. "Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence," PLOS Pathogens, Public Library of Science, vol. 15(12), pages 1-26, December.

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