HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α

Andrew W. Hardy, David R. Graham, Gene M. Shearer, Jean Philippe Herbeuval

Research output: Contribution to journalArticle

Abstract

Plasmacytoid dendritic cells (pDC) are key players in viral immunity and produce IFN-α after HIV-1 exposure, which in turn regulates TNF-related apoptosis-inducing ligand (TRAIL) expression by CD4+ T cells. We show here that infectious and noninfectious HIV-1 virions induce activation of pDC into TRAIL-expressing IFN-producing killer pDC (IKpDC). IKpDC expressed high levels of activation markers (HLA-DR, CD80, CD83, and CD86) and the migration marker CCR7. Surprisingly, CXCR4 and CCR5 were down-regulated on IKpDC. We also show that HIV-1-induced IKpDC depended on Toll-like receptor 7 (TLR7) activation. HIV-1 or TLR7 agonist-exposed IKpDC induced apoptosis of the CD4+ T cell line SupT1 via the TRAIL pathway. Furthermore, IFN-α produced after HIV-induced TLR7 stimulation was responsible for TRAIL expression and the down-regulation of both CXCR4 and CCR5 by IKpDC. In contrast, activation and migration markers were not regulated by IFN-α. Finally, IFN-α increased the survival of IKpDC. We characterized a subset of pDC with a killer activity that is activated by endosomal-associated viral RNA and not by infection.

Original languageEnglish (US)
Pages (from-to)17453-17458
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Keywords

  • AT-2 HIV-1
  • Apoptosis
  • CCR5
  • CXCR4
  • Endocytosis

ASJC Scopus subject areas

  • General

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