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 Journal Articles uri icon

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abstract

  • ProblemSemen 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 StudyTGF‐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.ResultsActive 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.ConclusionTGF‐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.

authors

  • Kafka, Jessica K
  • Osborne, Brendan JW
  • Sheth, Prameet M
  • Nazli, Aisha
  • Dizzell, Sara
  • Huibner, Sanja
  • Kovacs, Colin
  • Verschoor, Chris P
  • Bowdish, Dawn
  • Kaul, Rupert
  • Kaushic, Charu

publication date

  • February 2015