Table 6_Time-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype.xlsx

Syphilis, caused by Treponema pallidum subsp. pallidum, is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable T. pallidum to establish and maintain infection. The vascular endothelium is critical for T. pallidum attachment, dissemination, and host immune response initiation; however, the molecular details of T. pallidum-endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on T. pallidum-exposed brain microvascular endothelial cells. These analyses showed T. pallidum exposure altered pathways related to extracellular matrix, growth factors, integrins, and Rho GTPases. The induced transcriptional response was consistent with endothelial to mesenchymal transition, a process involved in fetal development and vascular dysfunction. In cells exposed to T. pallidum, the primary transcription factor associated with this process (Snail) was increased at both the transcript and protein levels, and microscopy analyses demonstrate F-actin cellular contraction. This study provides a comprehensive understanding of the molecular responses of endothelial cells to T. pallidum and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.

梅毒由苍白密螺旋体苍白亚种（Treponema pallidum subsp. pallidum）引起，是亟待应对的全球公共卫生威胁。当前梅毒疫苗研发受阻于对苍白密螺旋体建立并维持感染的分子机制认知不足。血管内皮对于苍白密螺旋体的黏附、播散以及宿主免疫应答启动至关重要，但二者互作的分子细节仍未完全阐明。为深化相关认知，本研究对暴露于苍白密螺旋体的脑微血管内皮细胞开展了时序转录组分析。结果显示，苍白密螺旋体暴露可改变与细胞外基质、生长因子、整合素以及Rho GTP酶相关的信号通路。诱导产生的转录应答与内皮细胞-间充质转化（endothelial to mesenchymal transition）一致，该过程参与胎儿发育与血管功能异常。在暴露于苍白密螺旋体的细胞中，该过程的核心转录因子Snail的转录本与蛋白水平均出现上调，显微镜分析证实细胞出现纤维状肌动蛋白（F-actin）收缩。本研究全面阐明了内皮细胞对苍白密螺旋体的分子应答，并筛选出了可能与梅毒疾病症状相关的宿主信号通路，相关成果可为梅毒疫苗研发提供理论支撑。