Treponema pallidum induces the activation of endothelial cells via macrophage-derived exosomes

Arch Dermatol Res. 2019 Mar;311(2):121-130. doi: 10.1007/s00403-018-01888-4. Epub 2019 Feb 2.

Abstract

Recent studies have shown that exosomes play a role in pathogenesis and in the treatment of inflammatory diseases and tumours. We explored the effects of Treponema pallidum-induced macrophage-derived exosomes on vascular endothelial cells to determine whether they are involved in the pathogenesis of syphilis. A syphilis infection model was established using rabbits to harvest T. pallidum at the peak of proliferation. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy, western blot assays, and nanoparticle tracking analysis. Secreted cytokine levels and the adhesion and permeability of human umbilical vein endothelial cells were evaluated in a co-culture model using the extracted exosomes. The results of this study revealed that exosomes derived from T. pallidum-infected macrophages enhanced cell adhesion and permeability. The levels of the secreted cytokines, including ICAM-1, VCAM-1, VEGF, and IL-8 were higher in the experimental group than in the control group. Our findings suggest that exosomes derived from T. pallidum-infected macrophages affect the cell adhesion and permeability of vascular endothelial cells. These changes may play important roles in syphilis pathogenesis. This study is the first to reveal the effects of exosomes derived from T. pallidum-infected macrophages on the adhesion, permeability, and secreted cytokines of human umbilical vein endothelial cells.

Keywords: Endothelial cells; Exosome; Macrophage; Syphilis; Treponema pallidum.

MeSH terms

  • Animals
  • Capillary Permeability
  • Cell Adhesion
  • Cell Communication
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endothelial Cells / microbiology
  • Endothelial Cells / physiology*
  • Exosomes / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macrophages / metabolism*
  • Rabbits
  • Signal Transduction
  • Syphilis / immunology*
  • Treponema pallidum / physiology*

Substances

  • Cytokines