Treponema pallidum induces pro-inflammatory cytokine secretion in macrophages and macrophage-endothelial co-cultures

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dc.contributor.authorWaugh, Sean
dc.contributor.authorRanasinghe, Akash
dc.contributor.authorReynolds, Lisa A.
dc.contributor.authorCameron, Caroline E.
dc.date.accessioned2026-05-07T17:31:19Z
dc.date.available2026-05-07T17:31:19Z
dc.date.issued2025
dc.description.abstractSyphilis, caused by the extracellular bacterium Treponema pallidum ssp. pallidum, is a multi-stage and systemic infection that is lifelong in the absence of treatment. Two host cell types that frequently encounter T. pallidum during infection are endothelial cells and macrophages; treponemes disseminate through the vasculature and cross the blood–brain and placental barriers by traversing endothelial cell barriers, and macrophages are known to be critical for clearance of T. pallidum. Despite the importance of macrophages in treponemal clearance and endothelial cells in treponemal dissemination, a comprehensive understanding of the cytokines secreted by T. pallidum-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?, MCP-1, GM-CSF, TNF, and IL-6 in T. pallidum-exposed macrophage monocultures and macrophage-endothelial cell co-cultures compared to the same culture conditions in the absence of T. pallidum. These investigations enhance our understanding of macrophage-mediated, T. pallidum-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, T. pallidum dissemination, and syphilis symptoms.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipThe author(s) declare financial support was received for the research and/or publication of this article. This work was supported by grants R37AI051334, U19AI144133, and U01AI182035 (CC) from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), as well as awards from Open Philanthropy (52345) and CIHR (506704 and 471857) to CC. SW is the recipient of a CIHR Canada Graduate Scholarship-Doctoral (CGS-D).
dc.identifier.citationWaugh S, Ranasinghe A, Reynolds LA and Cameron CE (2025) Treponema pallidum induces pro-inflammatory cytokine secretion in macrophages and macrophage-endothelial co-cultures. Frontiers in Cellular and Infection Microbiology, 15, 1681813. https://doi.org/10.3389/fcimb.2025.1681813
dc.identifier.urihttps://doi.org/10.3389/fcimb.2025.1681813
dc.identifier.urihttps://hdl.handle.net/1828/23850
dc.language.isoen
dc.publisherFrontiers in Cellular and Infection Microbiology
dc.rightsCC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSexual and Reproductive Health and Rights (SRHR) Aspiration Research Cluster
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleTreponema pallidum induces pro-inflammatory cytokine secretion in macrophages and macrophage-endothelial co-cultures
dc.typeArticle

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