Regulation of TNF-related apoptosis-inducing ligand on primary CD4 + T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells - 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 : 2005

Regulation of TNF-related apoptosis-inducing ligand on primary CD4 + T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

Andrew Hardy
  • Fonction : Auteur
Adriano Boasso
  • Fonction : Auteur
Stephanie Anderson
  • Fonction : Auteur
Matthew Dolan
  • Fonction : Auteur
Michel Dy
  • Fonction : Auteur

Résumé

TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, was suggested to contribute to HIV-1 pathogenesis by inducing CD4 + T cell death characteristic of AIDS. We previously reported HIV-1-mediated, TRAIL-induced apoptosis in primary CD4 + T cells in vitro and observed elevated levels of plasma TRAIL in HIV-1-infected patients. The present study elucidates the unresolved mechanism by which HIV-1 induces TRAIL expression on primary CD4 + T cells. We demonstrate that the expression of TRAIL by primary CD4 + T cells is regulated by IFN-α that is produced by HIV-1-stimulated plasmacytoid dendritic cells (pDCs). We also found that IFN-induced TRAIL is mediated by signal transducers and activators of transcription 1 and 2. We show that IFN-α production by HIV-1-activated pDCs is blocked by an early viral entry inhibitor of CD4-gp120 binding, but not by inhibitors of viral coreceptor binding. Our in vitro data are supported by the demonstration that anti-IFN-α and -β Abs inhibit apoptosis and TRAIL expression in CD4 + T cells from HIV-1-infected patients. Our findings suggest a potential unique role of pDCs in the immunopathogenesis of HIV-1 infection by inducing the death molecule TRAIL.

Dates et versions

hal-04198875 , version 1 (07-09-2023)

Identifiants

Citer

Jean-Philippe Herbeuval, Andrew Hardy, Adriano Boasso, Stephanie Anderson, Matthew Dolan, et al.. Regulation of TNF-related apoptosis-inducing ligand on primary CD4 + T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102 (39), pp.13974-13979. ⟨10.1073/pnas.0505251102⟩. ⟨hal-04198875⟩
2 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More