Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis
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 c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1254342/full |
| _version_ | 1797680778178461696 |
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| author | 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 Caroline E. Cameron |
| author_facet | 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 Caroline E. Cameron |
| author_sort | Sean Waugh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T23:35:13Z |
| format | Article |
| id | doaj.art-aafce8b765b64c3297f7d1cd1d8d04e1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-11T23:35:13Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-aafce8b765b64c3297f7d1cd1d8d04e12023-09-20T04:48:20ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-09-011410.3389/fmicb.2023.12543421254342Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesisSean Waugh0Akash Ranasinghe1Alloysius Gomez2Simon Houston3Karen V. Lithgow4Azad Eshghi5Jenna Fleetwood6Kate M. E. Conway7Lisa A. Reynolds8Caroline E. Cameron9Caroline E. Cameron10Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaUniversity of Victoria-Genome BC Proteomics Centre, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, United StatesIntroductionSyphilis 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1254342/fullsyphilisTreponema pallidumproteomicsdisseminationdisease symptoms |
| spellingShingle | 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 Caroline E. Cameron Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis Frontiers in Microbiology syphilis Treponema pallidum proteomics dissemination disease symptoms |
| 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 | syphilis Treponema pallidum proteomics dissemination disease symptoms |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1254342/full |
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