Potential mechanisms of Treponema pallidum breaching the blood-brain barrier

Syphilis, a sexually transmitted disease caused by Treponema pallidum subsp. pallidum (T. pallidum), can lead to a complication known as neurosyphilis. Neurosyphilis affects multiple components of the nervous system, including the meninges, blood vessels, brain parenchyma, and others, significantly impacting the central nervous system (CNS). Despite the effective control of syphilis spread by antibiotics, recent years have seen a resurgence in incidence among high-risk populations. The blood-brain barrier (BBB) is a critical defense for the CNS, preventing toxins and pathogens, including viruses, from entering and ensuring CNS function. The exact mechanisms of how T. pallidum penetrates the BBB are still not fully understood. Extensive research suggests that T. pallidum can disrupt endothelial cells and intercellular junctions, as well as induce abnormal activation of immune cells and aberrant cytokine expression, potentially facilitating its breach of BBB. Based on current research, we focus on the detrimental effects of cytokines on BBB integrity. We have also summarized the pathways T. pallidum uses to penetrate cellular barriers. Understanding the interaction between T. pallidum and the BBB is essential for revealing neurosyphilis pathogenesis and developing new therapies. DATA AVAILABILITY: Data used to support the findings of this study are included in the article.