Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis

梅毒与宿主:宿主细胞对梅毒螺旋体反应的多组学分析为梅毒发病机制提供了新的见解

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作者:Sean Waugh, Akash Ranasinghe, Alloysius Gomez, Simon Houston, Karen V Lithgow, Azad Eshghi, Jenna Fleetwood, Kate M E Conway, Lisa A Reynolds, Caroline E Cameron

Discussion

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 T. pallidum exposure and the pathogenic strategies used by T. pallidum to disseminate and persist within the host. Furthermore, our findings highlight the critical need for inclusion of appropriate controls when conducting T. pallidum-host cell interactions using in vitro- and in vivo-grown T. pallidum.

Methods

To address this knowledge gap, we used quantitative proteomics and cytokine profiling to characterize endothelial responses to T. pallidum.

Results

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 T. pallidum 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).

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