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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation*
  • Antigens, CD1 / metabolism
  • Ascites / etiology
  • Ascites / immunology
  • Blood Buffy Coat / cytology
  • Cell Culture Techniques
  • Cells, Cultured
  • Cross-Priming / immunology*
  • Cytosol / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Glycoproteins / metabolism
  • Healthy Volunteers
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / immunology
  • Palatine Tonsil / cytology
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Vacuoles / immunology
  • Vacuoles / metabolism*


  • Antigens, CD1
  • CD1C protein, human
  • Glycoproteins