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- W3161519114 abstract "Pathogens that establish intracellular niches may have evolved strategies to prevent their detection by cytotoxic CD8+ T lymphocytes (CTL), which in some cases requires antigen cross-presentation by dendritic cells (DC). Here, we asked whether Leishmania parasites minimize cross-priming of CD8+ T cells by triggering the SHP-1-FcRγ chain inhibitory axis described in DC expressing the C-type lectin receptor Mincle. We found a boosted early CTL response to Leishmania in mice deficient for Mincle, or with a selective loss of SHP-1 in CD11c+ cells, which also showed improved cross-presentation of vaccinia virus-derived antigens from infected cells. CTL activation in vitro revealed increased expression of MHC class I-peptide complexes by cross-presenting CD11c+ cells deficient for Mincle or SHP-1. Parasite treatment with neuraminidase also boosted cross-presentation, suggesting that Leishmania triggers sialic acid-binding receptors associated with SHP-1. Mechanistically, increased cross-presentation by SHP-1-deficient CD11c+ cells correlated with reduced endosomal acidification. Finally, we demonstrate that vaccination with GM-CSF bone marrow-derived cells treated with an SHP-1 inhibitor and loaded with Leishmania antigen inducesCD8+ T cell responses and confers protection in mice, overcoming the need for an adjuvant. Thus, SHP-1-mediated impairment of cross-presentation can be exploited by pathogens to evade CTLs, and functional SHP-1 inhibition improves CTL responses during vaccination." @default.
- W3161519114 created "2021-05-24" @default.
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- W3161519114 date "2020-01-01" @default.
- W3161519114 modified "2023-10-18" @default.
- W3161519114 title "<i>Leishmania</i> Triggering of SHP-1 in Dendritic Cells Inhibits Antigen Cross-Presentation to Cd8 <sup>+</sup> T Cells" @default.
- W3161519114 doi "https://doi.org/10.2139/ssrn.3645487" @default.
- W3161519114 hasPublicationYear "2020" @default.
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