{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:32:35Z","timestamp":1789623155453,"version":"build-2803163510"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Syphilis is a chronic, multi-stage infection caused by the extracellular bacterium\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      ssp.\n                      <jats:italic>pallidum<\/jats:italic>\n                      .\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      widely disseminates through the vasculature, crosses endothelial, blood\u2013brain and placental barriers, and establishes systemic infection. Although the capacity of\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      to traverse the endothelium is well-described, the response of endothelial cells to\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      exposure, and the contribution of this response to treponemal traversal, is poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To address this knowledge gap, we used quantitative proteomics and cytokine profiling to characterize endothelial responses to\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      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).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      exposure and the pathogenic strategies used by\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      to disseminate and persist within the host. Furthermore, our findings highlight the critical need for inclusion of appropriate controls when conducting\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      -host cell interactions using\n                      <jats:italic>in vitro-<\/jats:italic>\n                      and\n                      <jats:italic>in vivo-<\/jats:italic>\n                      grown\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2023.1254342","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:48:30Z","timestamp":1695170910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis"],"prefix":"10.3389","volume":"14","author":[{"given":"Sean","family":"Waugh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Ranasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alloysius","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen V.","family":"Lithgow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azad","family":"Eshghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Fleetwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M. E.","family":"Conway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1002\/ijc.22006","article-title":"Interleukin-6 induces both cell growth and VEGF production in malignant mesotheliomas","volume":"119","author":"Adachi","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"688388","DOI":"10.3389\/fcell.2021.688388","article-title":"Sinner or saint?: Nck adaptor proteins in vascular biology","volume":"9","author":"Alfaidi","year":"2021","journal-title":"Front. Cell Dev. 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