TY - JOUR
T1 - TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells
AU - Herbeuval, Jean Philippe
AU - Boasso, Adriano
AU - Grivel, Jean Charles
AU - Hardy, Andrew W.
AU - Anderson, Stephanie A.
AU - Dolan, Matthew J.
AU - Chougnet, Claire
AU - Lifson, Jeffrey D.
AU - Shearer, Gene M.
PY - 2005/3/15
Y1 - 2005/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=15244358107&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-08-3058
DO - 10.1182/blood-2004-08-3058
M3 - Article
C2 - 15585654
AN - SCOPUS:15244358107
SN - 0006-4971
VL - 105
SP - 2458
EP - 2464
JO - Blood
JF - Blood
IS - 6
ER -