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Nat Commun. 2018 Jul 2;9(1):2570. doi: 10.1038/s41467-018-04985-0.

Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway.

Author information

1
Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005, Paris, France.
2
Sanofi, Breakthrough Laboratory, 1 Impasse des Ateliers, 94400, Vitry-sur-Seine, France.
3
Institut Curie, PSL Research University, NGS Platform, 26 rue d'Ulm, 75005, Paris, France.
4
Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005, Paris, France. elodie.segura@curie.fr.

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 co-stimulatory signals to induce effector cytotoxic CD8+ T cells. Our findings thus provide important insights on how to harness cross-presentation for therapeutic purposes.

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