TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells

Jean Philippe Herbeuval, Adriano Boasso, Jean-Charles B. Grivel, Andrew W. Hardy, Stephanie A. Anderson, Matthew J. Dolan, Claire Chougnet, Jeffrey D. Lifson, Gene M. Shearer

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119 Citations (Scopus)

Abstract

There is now considerable in vitro evidence that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is involved in HIV-1 pathogenesis by inducing CD4+ T-cell death characteristic of AIDS. Therefore, we have tested levels of TRAIL in plasma samples from 107 HIV-1-infected and 53 uninfected controls as well as in longitudinal plasma samples from patients who started antiretroviral therapy (ART). TRAIL was elevated In plasma of HIV-1-infected patients compared with uninfected individuals, and patients receiving ART showed decreased plasma TRAIL levels that correlated with reduction in viral load. In vitro exposure to infectious and noninfectious HIV-1 induced TRAIL in monocytes and marginally in dendritic cells (DCs) but not in macrophages or T cells. Interestingly, the HIV-1 entry inhibitor, soluble CD4, blocked HIV-1-induced production of TRAIL. Furthermore, production and gene expression of TRAIL by monocytes were regulated by type I interferon via signal transducer and activator of transcription-1 (STAT1)/STAT2 signaling molecule. Ex vivo HIV-1 infection of human tonsil lymphoid tissue also resulted in increased TRAIL production. We demonstrate here that plasma TRAIL is elevated in HSV-1-infected patients and is decreased by ART therapy. The high production of TRAIL by antigen-presenting cells may contribute to the death of CD4+ T cells during progression to AIDS.

Original languageEnglish
Pages (from-to)2458-2464
Number of pages7
JournalBlood
Volume105
Issue number6
DOIs
Publication statusPublished - 15 Mar 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Herbeuval, J. P., Boasso, A., Grivel, J-C. B., Hardy, A. W., Anderson, S. A., Dolan, M. J., Chougnet, C., Lifson, J. D., & Shearer, G. M. (2005). TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells. Blood, 105(6), 2458-2464. https://doi.org/10.1182/blood-2004-08-3058