SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.

Autor:	Khouili SC; Immunobiology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain., Cook ECL; Department of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, Spain., Hernández-García E; Department of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, Spain., Martínez-López M; Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisboa, Portugal., Conde-Garrosa R; Immunobiology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain., Iborra S; Department of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, Spain. Electronic address: siborra@ucm.es.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Dec 01; Vol. 33 (9), pp. 108468.
DOI:	10.1016/j.celrep.2020.108468
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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