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dc.contributor.author | Alsina-Beauchamp, Dayanira | |
dc.contributor.author | Escos, Alejandra | |
dc.contributor.author | Fajardo, Pilar | |
dc.contributor.author | Gonzalez-Romero, Diego | |
dc.contributor.author | Diaz-Mora, Ester | |
dc.contributor.author | Risco, Ana | |
dc.contributor.author | Martin-Serrano, Miguel A. | |
dc.contributor.author | del Fresno, Carlos | |
dc.contributor.author | Dominguez-Andres, Jorge | |
dc.contributor.author | Aparicio, Noelia | |
dc.contributor.author | Zur, Rafal | |
dc.contributor.author | Shpiro, Natalia | |
dc.contributor.author | Brown, Gordon D. | |
dc.contributor.author | Ardavín, Carlos | |
dc.contributor.author | Netea, Mihai G | |
dc.contributor.author | Alemany, Susana | |
dc.contributor.author | Sanz-Ezquerro, Juan J. | |
dc.contributor.author | Cuenda, Ana | |
dc.date.accessioned | 2018-11-22T08:10:51Z | |
dc.date.available | 2018-11-22T08:10:51Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000431632400002 | |
dc.identifier.citation | EMBO Mol Med. 2018; 10(5):e8485 | |
dc.identifier.issn | 1757-4676 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6673 | |
dc.description.abstract | Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38 gamma and p38 delta regulate the innate immune response to C.albicans. We describe a new TAK1-TPL2-MKK1-ERK1/2 pathway in macrophages, which is activated by Dectin-1 engagement and positively regulated by p38 gamma/p38 delta. In mice, p38 gamma/p38 delta deficiency protects against C.albicans infection by increasing ROS and iNOS production and thus the antifungal capacity of neutrophils and macrophages, and by decreasing the hyper-inflammation that leads to severe host damage. Leucocyte recruitment to infected kidneys and production of inflammatory mediators are decreased in p38 beta/delta-null mice, reducing septic shock. p38 gamma/p38 delta in myeloid cells are critical for this effect. Moreover, pharmacological inhibition of p38 gamma/p38 delta in mice reduces fungal burden, revealing that these p38MAPKs may be therapeutic targets for treating C. albicans infection in humans. | |
dc.description.sponsorship | We thank P. Cohen for critically reading the manuscript. This work was supported by grants from the MINECO [SAF2013-45331-R and SAF2016-79792-R (AEI/FEDER, UE)] to AC and JJS-E, La Marato TV3 Foundation (20133431) to AC and (SAF2014-52009-R) to SA. ERC Consolidator Grant (\#310372) and a Spinoza grant of the Netherlands Organization for Scientific Research to MGN, and Wellcome Trust, the Medical Research Council (MRC; UK), the MRC Centre for Medical Mycology at the University of Aberdeen to GDB. DAB and AE receive MINECO FPI fellowships, AR a MINECO Juan de la Cierva award and JD-A a La Caixa Foundation PhD fellowship. | |
dc.language.iso | eng | |
dc.publisher | Wiley | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Candida albicans | |
dc.subject | Infection | |
dc.subject | Kinase inhibitor | |
dc.subject | p38MAPK | |
dc.subject | Signalling | |
dc.subject | PATTERN-RECOGNITION RECEPTORS | |
dc.subject | TNF-ALPHA PRODUCTION | |
dc.subject | LOCI-2 TPL2 KINASE | |
dc.subject | INNATE IMMUNITY | |
dc.subject | IN-VIVO | |
dc.subject | INVASIVE CANDIDIASIS | |
dc.subject | CROSS-TALK | |
dc.subject | INFLAMMATION | |
dc.subject | P38-GAMMA | |
dc.subject | P38-DELTA | |
dc.title | Myeloid cell deficiency of p38 gamma/p38 delta protects against candidiasis and regulates antifungal immunity | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 29661910 | |
dc.format.volume | 10 | |
dc.identifier.doi | 10.15252/emmm.201708485 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Dutch Research Council (Holanda) | |
dc.contributor.funder | Wellcome Trust | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.identifier.e-issn | 1757-4684 | |
dc.relation.publisherversion | https://doi.org/10.15252/emmm.201708485 | |
dc.identifier.journal | EMBO Molecular Medicine | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Inmunobiología | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-45331-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-79792-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/310372 | es_ES |
dc.rights.accessRights | open access | es_ES |