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00925njm 22002777a 4500 dc Khouili, Sofia C. author Cook, Emma CL author Hernández-García, Elena author Martínez-López, María author Conde-Garrosa, Ruth author Iborra, Salvador author 2020-12-03 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. Cell Rep. 2020; 33(9):108468 2211-1247 http://hdl.handle.net/20.500.12105/12750 33264612 10.1016/j.celrep.2020.108468 Cell reports SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.