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dc.contributor.author | Saz-Leal, Paula | |
dc.contributor.author | del Fresno, Carlos | |
dc.contributor.author | Brandi, Paola | |
dc.contributor.author | Martinez-Cano, Sarai | |
dc.contributor.author | Dungan, Otto M. | |
dc.contributor.author | Chisholm, John D. | |
dc.contributor.author | Kerr, William G. | |
dc.contributor.author | Sancho, David | |
dc.date.accessioned | 2018-11-22T08:10:49Z | |
dc.date.available | 2018-11-22T08:10:49Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000448675900002 | |
dc.identifier.citation | Cell Rep. 2018; 25(5):1118-1126 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6661 | |
dc.description.abstract | beta-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.sponsorship | We 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.iso | eng | |
dc.publisher | Cell Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | CANDIDA-ALBICANS INFECTION | |
dc.subject | IN-VIVO | |
dc.subject | INNATE IMMUNITY | |
dc.subject | MONOCYTES | |
dc.subject | PROTECTION | |
dc.subject | INFLAMMATION | |
dc.subject | REINFECTION | |
dc.subject | INDUCTION | |
dc.subject | VITRO | |
dc.title | Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection | |
dc.type | journal article | |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 30380404 | |
dc.format.volume | 25 | |
dc.format.page | 1118-1126 | |
dc.identifier.doi | 10.1016/j.celrep.2018.09.092 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Asociación Española Contra el Cáncer | |
dc.contributor.funder | Centro Nacional de Investigaciones Cardiovasculares Carlos III (España) | |
dc.contributor.funder | Agencia Estatal de Investigación (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fondation ACTERIA (Acting on European Research in Immunology and Allergology) | |
dc.contributor.funder | Atresmedia | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2018.09.092 | |
dc.identifier.journal | Cell Reports | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Inmunobiología | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/635122 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/725091 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BES-2015-072699 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD16/0015/0018-REEM | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-79040-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |