2026-04-29T12:25:15Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/127502025-04-01T10:23:56Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16938
Repisalud
author
Khouili, Sofia C.
author
Cook, Emma CL
author
Hernández-García, Elena
author
Martínez-López, María
author
Conde-Garrosa, Ruth
author
Iborra, Salvador
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
European Molecular Biology Organization
2021-04-23T09:26:35Z
2021-04-23T09:26:35Z
2020-12-03
Cell Rep. 2020; 33(9):108468
10.1016/j.celrep.2020.108468
2211-1247
Cell reports
33264612
http://hdl.handle.net/20.500.12105/12750
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.
eng
SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.
journal article
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