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- Title
Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway.
- Authors
Tsing-Lee Tang-Huau; Gueguen, Paul; Goudot, Christel; Durand, Mélanie; Bohec, Mylène; Baulande, Sylvain; Pasquier, Benoit; Amigorena, Sebastian; Segura, Elodie
- Abstract
Presentation of exogenous antigens on MHC-I molecules, termed cross-presentation, is essential for cytotoxic CD8+ T cell responses. In mice, dendritic cells (DCs) that arise from monocytes (mo-DCs) during inflammation have a key function in these responses by cross-presenting antigens locally in peripheral tissues. Whether human naturally-occurring mo-DCs can cross-present is unknown. Here, we use human mo-DCs and macrophages directly purified from ascites to address this question. Single-cell RNA-seq data show that ascites CD1c+ DCs contain exclusively monocyte-derived cells. Both ascites mo-DCs and monocyte-derived macrophages cross-present efficiently, but are inefficient for transferring exogenous proteins into their cytosol. Inhibition of cysteine proteases, but not of proteasome, abolishes cross-presentation in these cells. We conclude that human monocyte-derived cells cross-present exclusively using a vacuolar pathway. Finally, only ascites mo-DCs provide costimulatory signals to induce effector cytotoxic CD8+ T cells. Our findings thus provide important insights on how to harness cross-presentation for therapeutic purposes.
- Publication
Nature Communications, 2018, Vol 9, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04985-0