SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity
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 Min...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720314571 |
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| author | Sofía C. Khouili Emma C.L. Cook Elena Hernández-García María Martínez-López Ruth Conde-Garrosa Salvador Iborra |
| author_facet | Sofía C. Khouili Emma C.L. Cook Elena Hernández-García María Martínez-López Ruth Conde-Garrosa Salvador Iborra |
| author_sort | Sofía C. Khouili |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:30:52Z |
| format | Article |
| id | doaj.art-c59568341b2f4dc597b1bf14e68d210e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T18:30:52Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c59568341b2f4dc597b1bf14e68d210e2022-12-21T18:54:16ZengElsevierCell Reports2211-12472020-12-01339108468SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade ImmunitySofía C. Khouili0Emma C.L. Cook1Elena Hernández-García2María Martínez-López3Ruth Conde-Garrosa4Salvador Iborra5Immunobiology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, SpainDepartment of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, SpainDepartment of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, SpainChampalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisboa, PortugalImmunobiology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, SpainDepartment of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720314571dendritic cellsantigen cross-presentationLeishmaniaMincleSHP-1immune evasion |
| spellingShingle | Sofía C. Khouili Emma C.L. Cook Elena Hernández-García María Martínez-López Ruth Conde-Garrosa Salvador Iborra SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity Cell Reports dendritic cells antigen cross-presentation Leishmania Mincle SHP-1 immune evasion |
| title | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity |
| title_full | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity |
| title_fullStr | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity |
| title_full_unstemmed | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity |
| title_short | SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity |
| title_sort | shp 1 regulates antigen cross presentation and is exploited by leishmania to evade immunity |
| topic | dendritic cells antigen cross-presentation Leishmania Mincle SHP-1 immune evasion |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720314571 |
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