Waugh Sean, Ranasinghe Akash, Gomez Alloysius, Houston Simon, Lithgow Karen V, Eshghi Azad, Fleetwood Jenna, Conway Kate M E, Reynolds Lisa A, Cameron Caroline E
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
University of Victoria-Genome BC Proteomics Centre, Victoria, BC, Canada.
Front Microbiol. 2023 Sep 19;14:1254342. doi: 10.3389/fmicb.2023.1254342. eCollection 2023.
Syphilis is a chronic, multi-stage infection caused by the extracellular bacterium ssp. . widely disseminates through the vasculature, crosses endothelial, blood-brain and placental barriers, and establishes systemic infection. Although the capacity of to traverse the endothelium is well-described, the response of endothelial cells to exposure, and the contribution of this response to treponemal traversal, is poorly understood.
To address this knowledge gap, we used quantitative proteomics and cytokine profiling to characterize endothelial responses to .
Proteomic analyses detected altered host pathways controlling extracellular matrix organization, necroptosis and cell death, and innate immune signaling. Cytokine analyses of endothelial cells exposed to revealed increased secretion of interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF), and decreased secretion of monocyte chemoattractant protein-1 (MCP-1).
This study provides insight into the molecular basis of syphilis disease symptoms and the enhanced susceptibility of individuals infected with syphilis to HIV co-infection. These investigations also enhance understanding of the host response to exposure and the pathogenic strategies used by to disseminate and persist within the host. Furthermore, our findings highlight the critical need for inclusion of appropriate controls when conducting -host cell interactions using and grown .
梅毒是一种由细胞外细菌苍白密螺旋体亚种引起的慢性多阶段感染。苍白密螺旋体亚种通过脉管系统广泛传播，穿过内皮、血脑和胎盘屏障，并引发全身感染。尽管苍白密螺旋体穿过内皮的能力已有充分描述，但内皮细胞对苍白密螺旋体暴露的反应以及这种反应对密螺旋体穿越的贡献却知之甚少。
为填补这一知识空白，我们使用定量蛋白质组学和细胞因子谱分析来表征内皮细胞对苍白密螺旋体的反应。
蛋白质组学分析检测到宿主控制细胞外基质组织、坏死性凋亡和细胞死亡以及固有免疫信号传导的途径发生了改变。对暴露于苍白密螺旋体的内皮细胞进行的细胞因子分析显示，白细胞介素（IL）-6、IL-8和血管内皮生长因子（VEGF）的分泌增加，而单核细胞趋化蛋白-1（MCP-1）的分泌减少。
本研究深入探讨了梅毒疾病症状的分子基础以及梅毒感染者对HIV合并感染易感性增加的原因。这些研究还有助于加深对宿主对苍白密螺旋体暴露的反应以及苍白密螺旋体在宿主体内传播和持续存在所采用的致病策略的理解。此外，我们的研究结果突出表明，在使用培养的苍白密螺旋体进行宿主细胞相互作用研究时，迫切需要纳入适当的对照。
