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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1957-1964.
Prepublished online as a Blood First Edition Paper on May 16, 2006; DOI 10.1182/blood-2006-03-010918.
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Submitted March 17, 2006
Accepted May 4, 2006
Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition
Fedde Groot, Toni M van Capel, Martien L Kapsenberg, Ben Berkhout, and Esther C de Jong*
Academic Medical Center, University of Amsterdam
* Corresponding author; email: e.c.dejong{at}amc.uva.nl.
CD11c+ myeloid dendritic cells (DC) (MDC) and CD11c- CD123+ plasmacytoid DC (PDC) have been identified as main human DC subsets. MDC are professional antigen presenting cells for T cells, and include Langerhans cells, dermal DC and interstitial DC. They have been associated with HIV-1 capture and sexual transmission, whereas PDC play an important role in the innate immune responses to different types of viruses, including HIV-1. To compare the influence of MDC and PDC on HIV-1 infection of T cells, we isolated donor-matched MDC and PDC from peripheral blood, activated them by adding different maturation inducing compounds, and co-cultured them with T cells and HIV-1. We found that MDC 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, PDC inhibit HIV-1 replication in T cells through the secretion of IFN and an additional, unidentified small molecule. This study shows that the two main types of DC have opposing roles in HIV-1 infection of T cells.
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