| Autor: |
Sofía C. Khouili, Emma C.L. Cook, Elena Hernández-García, María Martínez-López, Ruth Conde-Garrosa, Salvador Iborra |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 33, Iss 9, Pp 108468- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2020.108468 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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