title: TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques.
abstract: In mice, CD8α(+) myeloid dendritic cells (mDC) optimally cross-present Ags to CD8(+) T cells and respond strongly to TLR3 ligands. Although equivalent DC have been identified by comparative genomic analysis and functional studies in humans as XCR1(+)CD141 (BDCA-3)(+)Clec9A(+)cell adhesion molecule 1(+) mDC, and in sheep as CD26(+) mDC, these cells remained elusive in nonhuman primates. To remedy this situation, we delineated precisely DC and monocyte populations by 12-color flow cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a new mDC population, with strong phenotypic and transcriptional homology to human CD141(+) and murine CD8α(+) mDC, including XCR1 membrane expression as a conserved specific marker. In contrast, high CD11c expression was not characteristic of mDC in macaques, but of CD16(+) monocytes. Like their human and murine homologs, simian XCR1(+) mDC had much stronger responses to TLR3 stimulation than other myeloid cells. The importance of this new mDC population was tested in SIV(mac251) infection, the most relevant animal model for pathogenic HIV-1 infection and vaccination. This population increased sharply and transiently during acute infection, but was reduced in blood and spleen during advanced disease. The identification of XCR1(+) mDC in rhesus macaques opens new avenues for future preclinical vaccinal studies and highlights XCR1 as a prime candidate for targeted vaccine delivery.
authors.affiliation: INSERM Unité 1016, Institut Cochin, 75014 Paris, France;
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Dutertre
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Jourdain
authors.forename: Magali
authors.initials: M
authors.lastname: Rancez
authors.forename: Sonia
authors.initials: S
authors.lastname: Amraoui
authors.forename: Even
authors.initials: E
authors.lastname: Fossum
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Cindy
authors.initials: C
authors.lastname: Sanchez
authors.forename: Anne
authors.initials: A
authors.lastname: Couëdel-Courteille
authors.forename: Yolande
authors.initials: Y
authors.lastname: Richard
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Vincent
authors.initials: V
authors.lastname: Feuillet
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.forename: Anne
authors.initials: A
authors.lastname: Hosmalin
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D051196:Toll-Like Receptor 3