Plasmacytoid dendritic cells in HIV-1 infection

Jay A. Levy, UC San Francisco

Plasmacytoid dendritic cells (PDC), the major producers of type 1 interferons (IFN), are an important component of the innate immune response to HIV infection. During HIV infection, PDC levels in the blood are reduced, particularly in subjects with high viral load. This decrease in PDC numbers has been associated with opportunistic infections and disease. PDC can be induced to release IFN-α by high concentrations of HIV or by HIV-infected cells. In the latter case, IFN-α production by PDC suppresses HIV replication in the infected cells. These observations emphasize the important role the PDC can play in controlling HIV infection. An objective of this proposed study is to examine further the function of PDC in HIV-infected individuals at different clinical states by measuring relative levels of IFN-α production by PDC. Variations in this response could relate to HIV pathogenesis. Another objective is to define the exact mechanism(s) involved in PDC detection of HIV infection. We aim to identify the receptor(s) on these cells that recognize HIV infection and the viral antigenic components that stimulate this innate immune response. Bvisualize the processes involved in this PDC:HIV interaction.