title: Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells.
abstract: Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ-resident CD8(+) DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3(+) DCs were recently shown to be the homologues of mouse CD8(+) DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1(+) DCs, BDCA3(+) DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1(+) and BDCA3(+) DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ-resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U932, 75005 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Segura
authors.forename: Mélanie
authors.initials: M
authors.lastname: Durand
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D002469:Cell Separation; D045142:Cross-Priming / Q000276:immunology*; D003600:Cytosol / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology*; D058965:MART-1 Antigen / Q000276:immunology; D051379:Mice; D009336:Necrosis; D014066:Palatine Tonsil / Q000166:cytology; D010586:Phagocytes / Q000276:immunology*; D010588:Phagosomes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D008024:Ligands; D058965:MART-1 Antigen; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors