Open AccessDifferential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients
Author(s) -
Jean-Philippe Herbeuval,
Jakob Nilsson,
Adriano Boasso,
Andrew W. Hardy,
Michael J. Kruhlak,
Stephanie A. Anderson,
Matthew J. Dolan,
Michel Dy,
Jan Andersson,
Gene M. Shearer
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0600363103
Subject(s) - apoptosis , tumor necrosis factor alpha , pathogenesis , in vivo , biology , immunology , in vitro , intracellular , receptor , programmed cell death , cancer research , microbiology and biotechnology , biochemistry
Loss of CD4+ T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-α produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4+ T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN-α in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCsin vivo andin vitro . Expression of IFN-α was increased in lymphoid tonsillar tissue (LT) of patients with progressive (HIVprog ) compared with nonprogressive (HIVNP ) HIV-1 disease and to uninfected controls. LT from HIVprog exhibited higher TRAIL and DR5 mRNA levels than LT from HIVNP or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-α and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis.