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

INTRODUCTION: Syphilis 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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546344/
https://www.ncbi.nlm.nih.gov/pubmed/37795301
http://dx.doi.org/10.3389/fmicb.2023.1254342
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author 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.
author_facet 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.
author_sort Waugh, Sean
collection PubMed
description INTRODUCTION: Syphilis 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. 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). 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.
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spelling pubmed-105463442023-10-04 Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis 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. Front Microbiol Microbiology INTRODUCTION: Syphilis 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. 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). 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. Frontiers Media S.A. 2023-09-19 /pmc/articles/PMC10546344/ /pubmed/37795301 http://dx.doi.org/10.3389/fmicb.2023.1254342 Text en Copyright © 2023 Waugh, Ranasinghe, Gomez, Houston, Lithgow, Eshghi, Fleetwood, Conway, Reynolds and Cameron. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
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.
Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title_full Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title_fullStr Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title_full_unstemmed Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title_short Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
title_sort syphilis and the host: multi-omic analysis of host cellular responses to treponema pallidum provides novel insight into syphilis pathogenesis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546344/
https://www.ncbi.nlm.nih.gov/pubmed/37795301
http://dx.doi.org/10.3389/fmicb.2023.1254342
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