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

Tsing-Lee Tang-Huau, Paul Gueguen, Christel Goudot, Mélanie Durand, Mylène Bohec, Sylvain Baulande, Benoit Pasquier, Sebastian Amigorena and Elodie Segura ()
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Tsing-Lee Tang-Huau: Institut Curie, PSL Research University, INSERM, U932
Paul Gueguen: Institut Curie, PSL Research University, INSERM, U932
Christel Goudot: Institut Curie, PSL Research University, INSERM, U932
Mélanie Durand: Institut Curie, PSL Research University, INSERM, U932
Mylène Bohec: Institut Curie, PSL Research University, NGS Platform
Sylvain Baulande: Institut Curie, PSL Research University, NGS Platform
Benoit Pasquier: Sanofi, Breakthrough Laboratory
Sebastian Amigorena: Institut Curie, PSL Research University, INSERM, U932
Elodie Segura: Institut Curie, PSL Research University, INSERM, U932

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04985-0

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