Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition.
CD11c(+) myeloid dendritic cells (MDCs) and CD11c(-) CD123(+) plasmacytoid DCs (PDCs) have been identified as main human DC subsets. MDCs are professional antigen-presenting cells for T cells, and include Langerhans cells, dermal DCs, and interstitial DCs. They have been associated with HIV-1 capture and sexual transmission, whereas PDCs play an important role in the innate immune responses to different types of viruses, including HIV-1. To compare the influence of MDCs and PDCs on HIV-1 infection of T cells, we isolated donor-matched MDCs and PDCs from peripheral blood, activated them by adding different maturation-inducing compounds, and cocultured them with T cells and HIV-1. We found that MDCs enhance HIV-1 infection through capture of the virus and subsequent transmission to T cells, and that differently matured MDC subsets have different HIV-1 transmission efficiencies. These differences were not due to soluble factors, viral capture differences, or the expression of integrins ICAM-1, -2, -3, or LFA-1. In contrast, regardless of their state of maturation, PDCs inhibit HIV-1 replication in T cells through the secretion of IFNalpha and an additional, unidentified small molecule. This study shows that the 2 main types of DCs have opposing roles in HIV-1 infection of T cells.
Groot
Fedde
F
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
van Capel
Toni M M
TM
Kapsenberg
Martien L
ML
Berkhout
Ben
B
de Jong
Esther C
EC
D002460:Cell Line; D003713:Dendritic Cells / Q000145:classification* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014779:Virus Replication
D007370:Interferon Type I; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1