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dc.contributor.authorKhouili, Sofia C. 
dc.contributor.authorCook, Emma C L
dc.contributor.authorHernández-García, Elena
dc.contributor.authorMartínez-López, María
dc.contributor.authorConde-Garrosa, Ruth 
dc.contributor.authorIborra, S
dc.date.accessioned2021-04-23T09:26:35Z
dc.date.available2021-04-23T09:26:35Z
dc.date.issued2020-12-03
dc.identifier.citationCell Rep. 2020; 33(9):108468es_ES
dc.identifier.issn2211-1247es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12750
dc.description.abstractIntracellular pathogens have evolved strategies to evade detection by cytotoxic CD8+ T lymphocytes (CTLs). Here, we ask whether Leishmania parasites trigger the SHP-1-FcRγ chain inhibitory axis to dampen antigen cross-presentation in dendritic cells expressing the C-type lectin receptor Mincle. We find increased cross-priming of CTLs in Leishmania-infected mice deficient for Mincle or with a selective loss of SHP-1 in CD11c+ cells. The latter also shows improved cross-presentation of cell-associated viral antigens. CTL activation in vitro reveals increased MHC class I-peptide complex expression in Mincle- or SHP-1-deficient CD11c+ cells. Neuraminidase treatment also boosts cross-presentation, suggesting that Leishmania triggers SHP-1-associated sialic-acid-binding receptors. Mechanistically, enhanced antigen processing correlates with reduced endosomal acidification in the absence of SHP-1. Finally, we demonstrate that SHP-1 inhibition improves CD11c+ cell-based vaccination against the parasite. Thus, SHP-1-mediated impairment of cross-presentation can be exploited by pathogens to evade CTLs, and SHP-1 inhibition improves CTL responses during vaccination.es_ES
dc.description.sponsorshipWork in the S.I. laboratory is funded by the Spanish Ministerio de Ciencia e Innovación (MICINN), Agencia Estatal de Investigación, and Fondo Europeo de Desarrollo Regional (RTI2018-094484-B-I00 and RYC-2016-19463). S.C.K. is a recipient of a FPU fellowship (FPU16/03142) from the Spanish Ministry of Education, Culture and Sports. M.M.-L. is a recipient of an EMBO Long-Term Fellowship (EMBO LTF 463-2019).es_ES
dc.language.isoenges_ES
dc.publisherCell Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleSHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID33264612es_ES
dc.format.volume33es_ES
dc.format.number9es_ES
dc.format.page108468es_ES
dc.identifier.doi10.1016/j.celrep.2020.108468es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)es_ES
dc.contributor.funderEuropean Molecular Biology Organization (EMBO)es_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2020.108468es_ES
dc.identifier.journalCell reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Inmunobiologíaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RYC-2016-19463es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU16/03142es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/RTI2018-094484-B-I00es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional