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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.

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Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005, Paris, France.
Sanofi, Breakthrough Laboratory, 1 Impasse des Ateliers, 94400, Vitry-sur-Seine, France.
Institut Curie, PSL Research University, NGS Platform, 26 rue d'Ulm, 75005, Paris, France.
Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005, Paris, France.


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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