Distinct cytokine patterns in semen influence local HIV shedding and HIV target cell activation

J Infect Dis. 2014 Apr 15;209(8):1174-84. doi: 10.1093/infdis/jit649. Epub 2013 Nov 23.

Abstract

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 colony-stimulating 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 (G-CSF) concentrations were associated with T-cell activation. Cytokines in semen were highly coregulated in HIV-negative 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.

Keywords: HIV; T cells; activation; cytokines; inflammation; semen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / metabolism*
  • Flow Cytometry
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation / physiology
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Semen / metabolism
  • Semen / virology*
  • South Africa
  • T-Lymphocytes / immunology*
  • Virus Shedding / physiology*
  • Young Adult

Substances

  • Cytokines