Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells

J Virol. 2005 Jul;79(14):8861-9. doi: 10.1128/JVI.79.14.8861-8869.2005.

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) plays an important role in HIV-1 transmission and pathogenesis. Here, we studied the susceptibility of ex vivo-isolated CD11c+ myeloid DCs (MDCs) and CD123+ plasmacytoid DCs (PDCs) to HIV-1 infection and the function of these cells early after infection. Both DC subsets were susceptible to CCR5- and CXCR4-using HIV-1 isolates (BaL and IIIB, respectively). However, MDCs were more susceptible to HIV-1(BaL) infection than donor-matched PDCs. In addition, HIV-1(BaL) infected MDCs more efficiently than HIV-1(IIIB), whereas PDCs were equally susceptible to both isolates. While exposure to HIV-1 alone resulted in only weak maturation of DCs, Toll-like receptor 7/8 ligation induced full maturation in both infected and uninfected DCs. Maturation did not increase HIV-1 replication in infected DCs, and infected DCs retained their ability to produce tumor necrosis factor alpha after stimulation. Both HIV-1 isolates induced alpha interferon production exclusively in PDCs, irrespective of productive infection. In conclusion, PDCs and MDCs were susceptible to HIV-1 infection, but neither displayed functional defects as a consequence of infection. The difference in susceptibility of PDCs and MDCs to HIV-1 may have implications for HIV-1 transmission and DC-mediated transfer of HIV-1 to T cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dendritic Cells / virology*
  • HIV Core Protein p24 / analysis
  • HIV-1 / physiology*
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-12 / biosynthesis
  • Myeloid Cells / cytology
  • Myeloid Cells / virology*
  • Plasma Cells / cytology
  • Plasma Cells / virology*
  • Protein Subunits / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • HIV Core Protein p24
  • Imidazoles
  • Protein Subunits
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • resiquimod