Regulation of Chemotactic Effects on Brain Vascular Endothelial Cells by the Targeted Chemokine Receptor Signaling Pathway of Treponema pallidum

Yu Cui, Dan Shi, Juanjuan Ran, Jing Li, Ping Gu

Article ID: 7845
Vol 38, Issue 2, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243802.115
Received: 20 February 2024; Accepted: 20 February 2024; Available online: 20 February 2024; Issue release: 20 February 2024

Abstract

Background: Syphilis, an infectious disease caused by Treponema pallidum, poses a severe threat to the central nervous system (CNS). Despite the well-established affinity of the spirochete for the CNS, the specific regulatory mechanisms of Treponema pallidum on chemokine receptors in human brain microvascular endothelial cells (HBMEC) remain unclear. Therefore, our study aims to investigate the impact of Treponema pallidum on the expression of chemokine receptors in HBMEC, focusing on the chemokines Chemokine (C-X-C motif) Ligand 7 (CXCL7) and Chemokine (C-X-C motif) Ligand 13 (CXCL13). Methods: The serum samples from 60 neurosyphilis patients and 60 healthy controls were retrospectively analyzed. The HBMEC cells were exposed to active and inactivated Treponema pallidum and the expressions of chemokines (CXCL7 and CXCL13), both at gene and protein levels, were assessed using quantitative PCR (qPCR) and Western blot analysis. Additionally, Transwell migration assays were employed to investigate the impact on HL-60 cell chemotaxis. Results: Neurosyphilis patients exhibited elevated serum levels of CXCL7 and CXCL13 compared to controls. Exposure of HBMEC to active Treponema pallidum significantly increased the expression of CXCL7 and CXCL13 both at mRNA and protein levels. Moreover, active Treponema pallidum enhanced the chemotactic ability of HBMEC for HL-60 cells, while inactivated Treponema pallidum did not show any effect. Cell Counting Kit-8 (CCK8) assays revealed a significant decrease in HBMEC cell viability upon exposure to Treponema pallidum. Conclusion: Active Treponema pallidum upregulates CXCL7 and CXCL13 expression in HBMEC, promoting chemotaxis and enhancing the migratory potential of HL-60 cells. This suggests a potential role for these interactions in the pathogenesis of neurosyphilis. Future studies should consider more complex blood-brain barrier (BBB) models and assess the activation and phagocytic capabilities of migrated cells.


Keywords

syphilis;neurosyphilis;Treponema pallidum;blood-brain barrier;chemokines


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