Differential Expression of IFN-α and TRAIL/DR5 in Lymphoid Tissue of Progressor versus Nonprogressor HIV-1-Infected Patients

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 18; pp. 7000 - 7005
• Main Authors: Herbeuval, Jean-Philippe, Nilsson, Jakob, Boasso, Adriano, Hardy, Andrew W., Kruhlak, Michael J., Anderson, Stephanie A., Dolan, Matthew J., Dy, Michel, Andersson, Jan, Shearer, Gene M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.05.2006
• Subjects: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Adult; Antibodies; Apoptosis; Biological Sciences; Biology; Cultured cells; Cytokines; Dendritic Cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Disease Progression; fas Receptor; fas Receptor - metabolism; Female; Gene expression; HIV; HIV 1; HIV Infections; HIV Infections - immunology; HIV Infections - pathology; HIV Long-Term Survivors; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunology; Interferon Regulatory Factor-7; Interferon Regulatory Factor-7 - genetics; Interferon Regulatory Factor-7 - immunology; Interferon-alpha; Interferon-alpha - genetics; Interferon-alpha - metabolism; Life Sciences; Lymphoid Tissue; Lymphoid Tissue - cytology; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Male; Medicin och hälsovetenskap; Messenger RNA; Myeloid Differentiation Factor 88; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - metabolism; Signal transduction; T lymphocytes; Trails; Viral load; Virus Activation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600363103

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 pDCs in vivo and in vitro. Expression of IFN-α was increased in lymphoid tonsillar tissue (LT) of patients with progressive ($HIV_{prog}$) compared with nonprogressive ($HIV_{NP}$) HIV-1 disease and to uninfected controls. LT from$HIV_{prog}$exhibited higher TRAIL and DR5 mRNA levels than LT from$HIV_{NP}$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.