Latent TGF-β1 is compartmentalized between blood and seminal plasma of HIV-positive men and its activation in semen is negatively correlated with viral load and immune activation

Am J Reprod Immunol. 2015 Feb;73(2):151-61. doi: 10.1111/aji.12300. Epub 2014 Jul 23.

Abstract

Problem: Semen is the primary medium for sexual transmission of HIV-1 and contains high concentrations of TGF-β1, but its role in regulating HIV-mediated immune activation is unclear.

Method of study: TGF-β1 and sCD14 were compared in blood plasma (BP) and seminal plasma (SP) from HIV-uninfected and infected, antiretroviral therapy (ART)-naive and ART-treated men and in THP-1 cells following exposure to HIV-1. The relationship between TGF-β1 and sCD14 was determined by Spearman correlation.

Results: Active and latent forms of TGF-β1 were compartmentalized between BP and SP. Highest active TGF-β1 levels were present in SP of ART-naïve chronic-infected men and decreased following ART treatment. Latent TGF-β1 was upregulated in BP following HIV infection, and highest levels were observed in BP of acute-infected men. Similar expression trends were observed between latent TGF-β1 and sCD14 in BP. A significant negative correlation was observed between active TGF-β1, sCD14, and semen viral load in ART-naive men.

Conclusion: TGF-β1 is compartmentalized between blood and semen, possibly co-expressed with sCD14 by activated monocytes/macrophages in BP as a result of HIV infection. Conversion of latent TGF-β1 into its active form could contribute to regulation of viral load and immune activation in the male genital tract, but depends on the stage of infection.

Keywords: Blood plasma; HIV-1; TGF-β1; immune activation; sCD14; seminal plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • Cell Line
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Semen / immunology*
  • Transforming Growth Factor beta1 / blood*
  • Transforming Growth Factor beta1 / immunology
  • Viral Load
  • Young Adult

Substances

  • Anti-HIV Agents
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Transforming Growth Factor beta1