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dc.contributor.authorSaz-Leal, Paula 
dc.contributor.authordel Fresno, Carlos 
dc.contributor.authorBrandi, Paola 
dc.contributor.authorMartinez-Cano, Sarai 
dc.contributor.authorDungan, Otto M.
dc.contributor.authorChisholm, John D.
dc.contributor.authorKerr, William G.
dc.contributor.authorSancho, David 
dc.date.accessioned2018-11-22T08:10:49Z
dc.date.available2018-11-22T08:10:49Z
dc.date.issued2018
dc.identifierISI:000448675900002
dc.identifier.citationCell Rep. 2018; 25(5):1118-1126
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6661
dc.description.abstractbeta-Glucan-induced trained immunity in myeloid cells leads to long-term protection against secondary infections. Although previous studies have characterized this phenomenon, strategies to boost trained immunity remain undefined. We found that beta-glucan-trained macrophages from mice with a myeloid-specific deletion of the phosphatase SHIP-1 (LysM Delta SHIP-1) showed enhanced proinflammatory cytokine production in response to lipopolysaccharide. Following beta-glucan training, SHIP-1-deficient macrophages exhibited increased phosphorylation of Akt and mTOR targets, correlating with augmented glycolytic metabolism. Enhanced training in the absence of SHIP-1 relied on histone methylation and acetylation. Trained LysM Delta SHIP-1 mice produced increased amounts of proinflammatory cytokines upon rechallenge in vivo and were better protected against Candida albicans infection compared with control littermates. Pharmacological inhibition of SHIP-1 enhanced trained immunity against Candida infection in mouse macrophages and human peripheral blood mononuclear cells. Our data establish proof of concept for improvement of trained immunity and a strategy to achieve it by targeting SHIP-1.
dc.description.sponsorshipWe thank the members of the Immunobiology Lab for useful discussions. We thank the CNIC facilities and personnel, particularly Santiago Rodriguez and Ruben Mota, for their support. P.S.-L. is funded by grant BES-2015-072699 (´´Ayudas para Contratos Predoctorales para la Formacion de Doctores 2015´´) from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). C.d.F. is supported by the Asociacion Espanola Contra el Cancer (AECC) Foundation as a recipient of an ``Ayuda Fundacion Cientifica AECC a Personal Investigador en Cancer´´ grant. Work in the Sancho laboratory is funded by CNIC and grant SAF2016-79040-R from MINECO, Agencia Estatal de Investigacion, and FEDER (European Fund for Regional Development); grant B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; grant RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MINECO, and FEDER; Foundation Acteria; a Constantes y Vitales prize (Atresmedia); Foundation La Marato de TV3 (grant 201723); the European Commission (grant 635122-PROCROP H2020); and the European Research Council (ERC-2016-Consolidator Grant 725091). CNIC is supported by MINECO and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). W.G.K. is an Empire Scholar of the State of New York, the Murphy Family Professor of Children's Oncology Research, and is supported by funds from the Paige Arnold Butterfly Run.
dc.language.isoeng
dc.publisherCell Press 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCANDIDA-ALBICANS INFECTION
dc.subjectIN-VIVO
dc.subjectINNATE IMMUNITY
dc.subjectMONOCYTES
dc.subjectPROTECTION
dc.subjectINFLAMMATION
dc.subjectREINFECTION
dc.subjectINDUCTION
dc.subjectVITRO
dc.titleTargeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection
dc.typejournal article
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID30380404
dc.format.volume25
dc.format.page1118-1126
dc.identifier.doi10.1016/j.celrep.2018.09.092
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderCentro Nacional de Investigaciones Cardiovasculares Carlos III (España) 
dc.contributor.funderAgencia Estatal de Investigación (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderFondation ACTERIA (Acting on European Research in Immunology and Allergology) 
dc.contributor.funderAtresmedia 
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2018.09.092
dc.identifier.journalCell Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Inmunobiología
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/635122es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/725091es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2015-072699es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD16/0015/0018-REEMes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-79040-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional