Flt3L-Mediated Expansion of Plasmacytoid Dendritic Cells Suppresses HIV Infection in Humanized Mice

Cell Rep. 2019 Nov 26;29(9):2770-2782.e5. doi: 10.1016/j.celrep.2019.10.094.

Abstract

Plasmacytoid dendritic cells (plasmacytoid DC, pDC) are major IFN-I producers and have been shown to be affected by HIV through ill-defined mechanisms. In this study, we directly assess the role of pDC in early infection, evaluating whether modulating their abundance can alter viral replication. First, HIV infection of humanized mice induces systemic depletion of pDC, and in the presence of soluble FMS-like tyrosine kinase 3 ligand (Flt3L), pDC levels remain elevated. Flt3L significantly delays the onset of viremia and reduces viral replication via a process that is dependent on pDC and mediated through an enhanced early IFN-I response. pDC from Flt3L-treated mice are more prone to express IFN-α following TLR7 stimulation, but this propensity is gradually decreased during infection. In conclusion, maintaining pDC levels and function is key to effective early viral control, and in this context, these findings provide practical insights for anti-HIV strategies and vaccine design.

Keywords: FLT3L; IFN-I; TLR7 stimulation; acute HIV infection; antiviral response; hu-mice; pDC dysfunction; pDCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • HIV Infections / virology*
  • HIV-1 / pathogenicity*
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Virus Replication / immunology*

Substances

  • Membrane Proteins
  • flt3 ligand protein