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P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis

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dc.contributor.authorMartínez García, Juan José
dc.contributor.authorMartínez Banaclocha, Helios
dc.contributor.authorAngosto Bazarra, Diego
dc.contributor.authorTorre Minguela, Carlos de
dc.contributor.authorBaroja Mazo, Alberto
dc.contributor.authorAlarcón Vila, Cristina
dc.contributor.authorMartínez Alarcón, Laura
dc.contributor.authorAmores Iniesta, Joaquín
dc.contributor.authorMartín Sánchez, Fátima
dc.contributor.authorErcole, Giovanni A.
dc.contributor.authorMartínez, Carlos M.
dc.contributor.authorGonzález Lisorge, Ada
dc.contributor.authorFernández Pacheco, José
dc.contributor.authorMartínez Gil, Piedad
dc.contributor.authorAdriouch, Sahil
dc.contributor.authorKoch Nolte, Friedrich
dc.contributor.authorLuján, Juan
dc.contributor.authorAcosta Villegas, Francisco
dc.contributor.authorParrilla, Pascual
dc.contributor.authorGarcía Palenciano, Carlos
dc.contributor.authorPelegrín, Pablo
dc.contributor.departmentSanidad Animal
dc.date.accessioned2024-10-18T06:46:19Z
dc.date.available2024-10-18T06:46:19Z
dc.date.issued2019-06-20
dc.description© The Author(s) 2019. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in Nature Communications. To access the final edited and published work see https://doi.org/10.1038/s41467-019-10626-xes
dc.description.abstractSepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.es
dc.formatapplication/pdfes
dc.format.extent14es
dc.identifier.doihttps://doi.org/10.1038/s41467-019-10626-x
dc.identifier.eisbnNature Communications, 2019, Vol. 10: 2711es
dc.identifier.issnElectronic: 2041-1723
dc.identifier.urihttp://hdl.handle.net/10201/145421
dc.languageenges
dc.publisherNature Researches
dc.relationThis work was supported by grants from Instituto Salud Carlos III–Fondo Europeo de Desarrollo Regional (PI13/00174 to P.Pe.), Ministerio de Economia, Industria y Competitividad–Fondo Europeo de Desarrollo Regional (SAF2017-88276-R to P.Pe.), Fundación Séneca (20859/PI/18 to P.Pe.) and European Research Council (ERC-2013-CoG 614578 to P.Pe.).es
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-019-10626-x#Abs1es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleP2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsises
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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