Distinct Cytokine Patterns in Semen Influence Local HIV Shedding and HIV Target Cell Activation

• Published in: The Journal of infectious diseases 2014-04, Vol.209 (8), p.1174-1184
• Main Authors: Olivier, Abraham J., Masson, Lindi, Ronacher, Katharina, Walzl, Gerhard, Coetzee, David, Lewis, David A., Williamson, Anna-Lise, Passmore, Jo-Ann S., Burgers, Wendy A.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blood; Blood plasma; Cytokines; Cytokines - metabolism; Cytomegalovirus; Flow Cytometry; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV infections; HIV Infections - immunology; HIV-1 - physiology; HIV/AIDS; Human immunodeficiency virus; Humans; Infectious diseases; Inflammation; Lymphocyte Activation - physiology; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Real-Time Polymerase Chain Reaction; Semen - metabolism; Semen - virology; South Africa; T lymphocytes; T-Lymphocytes - immunology; Viral load; Virology; Virus Shedding - physiology; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit649

Background. Semen is the main vector for human immunodeficiency virus (HIV) transmission from men to women. We investigated the influence of cytokines in semen on local HIV burden and activated T cells. Methods. Blood and semen were collected from 42 HIV-negative and 38 HIV-positive men. Concentrations of 20 cytokines were measured by Luminex, and frequencies of activated T cells were measured by flow cytometry. Results. Semen contained higher concentrations of proinflammatory (monocyte chemotactic protein-1, interleukin [IL]-8, IL-6, Fractalkine, macrophage inflammatory protein (MIP)-1β, granulocyte macrophage colonystimulating factor) and adaptive cytokines (IL-7 and IL-15) and higher frequencies of activated T cells compared to blood. Plasma IL-2, eotaxin, MIP-1β, and IL-15 and semen eotaxin and granulocyte colony-stimulating factor (GCSF) concentrations were associated with T-cell activation. Cytokines in semen were highly coregulated in HIVnegative men; however, this network was disrupted during HIV infection. Several cytokines in semen correlated with HIV shedding (G-CSF, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], IL-10). Conclusion. Higher levels of inflammation and T-cell activation were observed in semen compared with blood. Seminal G-CSF, which influences neutrophil survival, T-cell function, and dendritic cell activation, was associated with T-cell activation and HIV shedding and may be an important target for reducing HIV shedding or risk.