<i>Treponema pallidum</i> ’s neural invasion: from blood-brain barrier breach to immune sabotage

Neurosyphilis is an infectious disease of the nervous system caused by <i>Treponema pallidum</i>. With the resurgence of syphilis worldwide, neurosyphilis has become prevalent again, but research on its pathogenesis remains challenging. <i>T. pallidum</i> exhibits remarkable invasive potential and immune evasion properties, which enable it to rapidly penetrate the blood-brain barrier (BBB) and infiltrate the central nervous system. Meanwhile, the immune response induced by this pathogen may cause tissue damage and accelerate disease progression. Additionally, host factors and the genotypes of <i>T. pallidum</i> strains are associated with susceptibility to neurosyphilis. This review systematically summarizes the latest literature on neurosyphilis, outlines recent advances in research on the effects of <i>T. pallidum</i> on the BBB, its immune interactions with the host, and omics-related studies, and aims to provide directions for future research on the pathogenesis of neurosyphilis.