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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.

Syphilis is a sexually transmitted disease caused by the infection of Treponema pallidum subspecies pallidum. T-helper type 17-related genes, vitamin D receptor (VDR) gene, and chemokine/chemokine receptor genes are crucial in microbial infection. A total of 16 single-nucleotide polymorphisms (SNPs) in eight genes (interleukin [IL]-17A, IL-17F, IL-23R, VDR, C-C motif chemokine ligand [CCL] 2, CCL5, C-C chemokine receptor [CCR] 2, and CCR5) were analyzed in 188 patients with syphilis and 216 healthy controls. The results showed a strong correlation of IL-17A rs2275913 (AA vs AG + GG: odds ratio [OR], 1.78; 95% confidence interval [CI], 1.09 to 2.92; P = 0.020; A vs G: OR, 1.33; 95% CI, 1.01 to 1.76; P = 0.043) and rs3819024 (GG vs AA + GA: OR, 1.76; 95% CI, 1.06 to 2.91; P = 0.028; G vs A: OR, 1.36; 95% CI, 1.03 to 1.80; P = 0.030) with syphilis. In haplotype analysis, IL-17A rs2275913A/rs3819024G showed a risk effect (OR, 1.38; 95% CI, 1.04 to 1.82; P = 0.026), whereas IL-17A rs2275913G/rs3819024A showed a protective effect (OR, 0.76; 95% CI, 0.57 to 0.998; P = 0.048). The expression levels of IL-17A messenger RNA (mRNA) in peripheral blood mononuclear cells and IL-17A secretion in plasma were further examined. No significant differences were found between patients with syphilis and healthy controls. The study also explored whether IL-17A rs2275913 and rs3819024 were associated with the expression of IL-17A mRNA and IL-17A secretion in patients with syphilis. Similar negative results were found. In conclusion, the polymorphisms of IL-17A rs2275913 and rs3819024 and the haplotype containing these two SNPs influenced the susceptibility to syphilis in a Han Chinese population., (© 2018 Wiley Periodicals, Inc.)