{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:32:30Z","timestamp":1789623150355,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R37AI051334, U19AI144133, U01AI182035"],"award-info":[{"award-number":["R37AI051334, U19AI144133, U01AI182035"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["506704, 471857"],"award-info":[{"award-number":["506704, 471857"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014895","name":"Open Philanthropy Project","doi-asserted-by":"publisher","award":["52345"],"award-info":[{"award-number":["52345"]}],"id":[{"id":"10.13039\/100014895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008997","name":"University of Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Syphilis, caused by the extracellular bacterium\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    ssp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    , is a multi-stage and systemic infection that is lifelong in the absence of treatment. Two host cell types that frequently encounter\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    during infection are endothelial cells and macrophages; treponemes disseminate through the vasculature and cross the blood\u2013brain and placental barriers by traversing endothelial cell barriers, and macrophages are known to be critical for clearance of\n                    <jats:italic>T. pallidum.<\/jats:italic>\n                    Despite the importance of macrophages in treponemal clearance and endothelial cells in treponemal dissemination, a comprehensive understanding of the cytokines secreted by\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    -exposed macrophages in the presence and absence of endothelial cells has not yet been achieved. To address this knowledge gap, we conducted time-course cytokine secretion profiling of macrophage-differentiated THP-1 cells alone and in co-culture with human brain microvascular endothelial cells. These experiments revealed reduced IL-8 secretion and increased secretion of RANTES, soluble ICAM-1, IL-1\u03b2, MCP-1, GM-CSF, TNF, and IL-6 in\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    -exposed macrophage monocultures and macrophage-endothelial cell co-cultures compared to the same culture conditions in the absence of\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    . These investigations enhance our understanding of macrophage-mediated,\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    -focused innate immune responses occurring at endothelial sites. Further, this study provides insight into pro-inflammatory mechanisms elicited after exposure to this pathogen that may contribute to endothelial junction disruption,\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    dissemination, and syphilis symptoms.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2025.1681813","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:31:24Z","timestamp":1760679084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Treponema pallidum induces pro-inflammatory cytokine secretion in macrophages and macrophage-endothelial co-cultures"],"prefix":"10.3389","volume":"15","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":"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":[[2025,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.14745\/ccdr.v48i23a01","article-title":"Rising syphilis rates in Canada, 2011\u20132020","volume":"48","author":"Aho","year":"2022","journal-title":"Can. 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