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

Frontiers in Microbiology

Microbiology

Sean Waugh¹  Lisa A. Reynolds¹  Karen V. Lithgow¹  Jenna Fleetwood¹  Simon Houston¹  Kate M. E. Conway¹  Akash Ranasinghe¹  Alloysius Gomez¹  Caroline E. Cameron²  Azad Eshghi³ 

[1] Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada;Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada;Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, United States;University of Victoria-Genome BC Proteomics Centre, Victoria, BC, Canada;

关键词: syphilis;    Treponema pallidum;    proteomics;    dissemination;    disease symptoms;   

DOI  :  10.3389/fmicb.2023.1254342

 received in 2023-07-07, accepted in 2023-09-01,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionSyphilis is a chronic, multi-stage infection caused by the extracellular bacterium Treponema pallidum ssp. pallidum. Treponema pallidum widely disseminates through the vasculature, crosses endothelial, blood–brain and placental barriers, and establishes systemic infection. Although the capacity of T. pallidum to traverse the endothelium is well-described, the response of endothelial cells to T. pallidum exposure, and the contribution of this response to treponemal traversal, is poorly understood.MethodsTo address this knowledge gap, we used quantitative proteomics and cytokine profiling to characterize endothelial responses to T. pallidum.ResultsProteomic 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).DiscussionThis 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.

【 授权许可】

Unknown   
Copyright © 2023 Waugh, Ranasinghe, Gomez, Houston, Lithgow, Eshghi, Fleetwood, Conway, Reynolds and Cameron.