HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2007

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 Hardy
  • Fonction : Auteur
David Graham
  • Fonction : Auteur
Gene Shearer
  • Fonction : Auteur

Résumé

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 agonistexposed 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.

Dates et versions

hal-04204737 , version 1 (12-09-2023)

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Citer

Andrew Hardy, David Graham, Gene Shearer, Jean-Philippe Herbeuval. HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (44), pp.17453-17458. ⟨10.1073/pnas.0707244104⟩. ⟨hal-04204737⟩
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