Systemic Immune Activation in HIV Infection Is Associated with Decreased MDC Responsiveness to TLR Ligand and Inability to Activate Naive CD4 T-Cells

• Published in: PloS one Vol. 6; no. 9; p. e23884
• Main Authors: Yonkers, Nicole L., Rodriguez, Benigno, Asaad, Robert, Lederman, Michael M., Anthony, Donald D.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Antiviral agents; B7-2 Antigen - metabolism; Cardiovascular disease; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD83 antigen; CD86 antigen; Cell activation; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - secretion; gamma -Interferon; Health aspects; Histocompatibility antigen HLA; HIV; HIV infections; HIV Infections - immunology; HIV Seropositivity - immunology; HLA-DR Antigens - metabolism; Human immunodeficiency virus; Humans; Immune response; Immune system; Infection; Infections; Interferon; Interleukin 2; Interleukin 6; Interleukin-6 - secretion; Ligands; Lymphocytes T; Male; Medicine; Middle Aged; Myeloid Cells - immunology; Pathogens; Phenotype; Poly I-C - immunology; Proteins; T cell receptors; T cells; Toll-like receptors; Toll-Like Receptors - metabolism; Up-Regulation - immunology; Viruses; Young Adult; Cleveland Ohio; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023884

HIV infection is characterized by ineffective anti-viral T-cell responses and impaired dendritic cell (DC) functions, including response to Toll-Like Receptor (TLR) ligands. Because TLR responsiveness may affect a host's response to virus, we examined TLR ligand induced Myeloid and Plasmacytoid DC (MDC and PDC) activation of naïve T-cells in HIV+ subjects. Freshly purified MDC and PDC obtained from HIV+ subjects and healthy controls were cultured in the presence and absence of TLR ligands (poly I∶C or R-848). We evaluated indices of maturation/activation (CD83, CD86, and HLA-DR expression), cytokine secretion (IFN-alpha and IL-6), and ability to activate allogeneic naïve CD4 T-cells to secrete IFN-gamma and IL-2. MDC from HIV+ subjects had increased spontaneous IL-6 production and increased CD83 and CD86 expression when compared to MDC of controls. MDC IL-6 expression was associated with plasma HIV level. At the same time, poly I∶C induced HLA-DR up-regulation on MDC was reduced in HIV+ persons when compared to controls. The latter finding was associated with impaired ability of MDC from HIV+ subjects to activate allogeneic naïve CD4 T-cells. PDC from HIV+ persons had increased spontaneous and TLR ligand induced IL-6 expression, and increased HLA-DR expression at baseline. The latter was associated with an intact ability of HIV PDC to activate allogeneic naïve CD4 T-cells. These results have implications for the ability of the HIV+ host to form innate and adaptive responses to HIV and other pathogens.