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 language | English (US) |
---|---|
Pages (from-to) | 17453-17458 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Issue number | 44 |
DOIs | |
State | Published - Oct 30 2007 |
Keywords
- AT-2 HIV-1
- Apoptosis
- CCR5
- CXCR4
- Endocytosis
ASJC Scopus subject areas
- General