Transforming growth factor beta 1 up-regulates CD169 (sialoadhesin) expression on monocyte-derived dendritic cells: role in HIV sexual transmission.

Abstract

Recent data describe CD169 (also called sialoadhesin or Siglec-1) as the main HIV-1 receptor expressed by mucosal dendritic cells involved in the capture of the virus and its transmission to target cells. In this study, we investigated the effect of transforming growth factor beta 1 (TGF-β1), a cytokine found in abundance in semen, on the expression of CD169 on dendritic cells in order to characterize its potential role in the capture of HIV-1 particles by these antigen-presenting cells. Monocyte-derived dendritic cells (MDDCs) were cultured in the presence of lipopolysaccharide, pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)] or different concentrations of TGF-β1, and analyzed for maturation marker and Siglec expression. The ability of MDDCs to capture HIV particles following the different treatments was also analyzed. TGF-β1 treatment promotes a significant increase of CD169 expression on MDDCs. This effect was specific since neither DC-SIGN nor other Siglec expressions were changed. The CD169 increase was due to a de-novo synthesis as evidenced by Western blot experiment. This up-regulation was well correlated to the concentration of TGF-β1 and associated with an increase of the MDDC ability to bind HIV particles. Interestingly, this phenomenon was independent of the maturation status of MDDCs. This study demonstrates that the most abundant cytokine present in semen (TGF-β1) is able to enhance specifically the expression of an important molecule (CD169) involved in the capture and transmission of HIV-1 particles from the mucosal lumen to the submucosal compartment. Our results suggest that this mechanism may play a relevant role in sexual HIV transmission.