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

Cell Reports

María Martínez-López¹  Emma C.L. Cook²  Elena Hernández-García²  Salvador Iborra²  Ruth Conde-Garrosa³  Sofía C. Khouili³ 

[1] Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisboa, Portugal;Department of Immunology, School of Medicine, Universidad Complutense de Madrid, 12 de Octubre Health Research Institute (imas12), Madrid, Spain;Immunobiology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain;

关键词: dendritic cells;    antigen cross-presentation;    Leishmania;    Mincle;    SHP-1;    immune evasion;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown