Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition

• Published in: Blood 2006-09, Vol.108 (6), p.1957-1964
• Main Authors: Groot, Fedde, van Capel, Toni M.M., Kapsenberg, Martien L., Berkhout, Ben, de Jong, Esther C.
• Format: Article
• Language: English
• Subjects: Cell Line; Dendritic Cells - classification; Dendritic Cells - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; HIV-1 - pathogenicity; HIV-1 - physiology; Humans; Immunity, Innate; In Vitro Techniques; Intercellular Adhesion Molecule-1 - metabolism; Interferon Type I - metabolism; Myeloid Cells - classification; Myeloid Cells - immunology; Receptors, CCR5 - metabolism; Receptors, CXCR4 - metabolism; Virus Replication
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-03-010918

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 IFNα 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.