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10.1038/s41467-018-04985-0

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suck abstract from ncbi


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pmid29967419
      Nat+Commun 2018 ; 9 (1 ): 2570
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  • Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway #MMPMID29967419
  • Tang-Huau TL ; Gueguen P ; Goudot C ; Durand M ; Bohec M ; Baulande S ; Pasquier B ; Amigorena S ; Segura E
  • Nat Commun 2018[Jul]; 9 (1 ): 2570 PMID29967419 show ga
  • 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.
  • |*Antigen Presentation [MESH]
  • |Antigens, CD1/metabolism [MESH]
  • |Ascites/etiology/immunology [MESH]
  • |Blood Buffy Coat/cytology [MESH]
  • |Cell Culture Techniques [MESH]
  • |Cells, Cultured [MESH]
  • |Cross-Priming/*immunology [MESH]
  • |Cytosol/metabolism [MESH]
  • |Dendritic Cells/*immunology/metabolism [MESH]
  • |Female [MESH]
  • |Gene Expression Profiling [MESH]
  • |Glycoproteins/metabolism [MESH]
  • |Healthy Volunteers [MESH]
  • |Humans [MESH]
  • |Macrophages/*immunology/metabolism [MESH]
  • |Male [MESH]
  • |Monocytes/*immunology/metabolism [MESH]
  • |Ovarian Neoplasms/complications/immunology [MESH]
  • |Palatine Tonsil/cytology [MESH]
  • |Sequence Analysis, RNA [MESH]
  • |Single-Cell Analysis [MESH]
  • |T-Lymphocytes, Cytotoxic/immunology/metabolism [MESH]


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