| First Author | C Khouili S | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 9 | Pages | 108468 |
| PubMed ID | 33264612 | Mgi Jnum | J:300595 |
| Mgi Id | MGI:6489090 | Doi | 10.1016/j.celrep.2020.108468 |
| Citation | C Khouili S, et al. (2020) SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity. Cell Rep 33(9):108468 |
| abstractText | Intracellular pathogens have evolved strategies to evade detection by cytotoxic CD8(+) T lymphocytes (CTLs). Here, we ask whether Leishmania parasites trigger the SHP-1-FcRgamma 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. |
