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dc.contributor.author | Khouili, Sofia C. | |
dc.contributor.author | Cook, Emma C L | |
dc.contributor.author | Hernández-García, Elena | |
dc.contributor.author | Martínez-López, María | |
dc.contributor.author | Conde-Garrosa, Ruth | |
dc.contributor.author | Iborra, Salvador | |
dc.date.accessioned | 2021-04-23T09:26:35Z | |
dc.date.available | 2021-04-23T09:26:35Z | |
dc.date.issued | 2020-12-03 | |
dc.identifier.citation | Cell Rep. 2020; 33(9):108468 | es_ES |
dc.identifier.issn | 2211-1247 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12750 | |
dc.description.abstract | Intracellular 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.sponsorship | Work 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.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 33264612 | es_ES |
dc.format.volume | 33 | es_ES |
dc.format.number | 9 | es_ES |
dc.format.page | 108468 | es_ES |
dc.identifier.doi | 10.1016/j.celrep.2020.108468 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | |
dc.contributor.funder | European Molecular Biology Organization | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2020.108468 | es_ES |
dc.identifier.journal | Cell reports | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Inmunobiología | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RYC-2016-19463 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FPU16/03142 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/RTI2018-094484-B-I00 | es_ES |
dc.rights.accessRights | open access | es_ES |