Syphilis Pathogenesis: Host Immune Response versus Pathogen Immune Evasion.

Syphilis, caused by Treponema pallidum subspecies pallidum (T. pallidum), remains a significant global health problem despite being preventable and curable. The pathogen's ability to evade the immune system using virulence factor-based strategies and by invading immune-privileged sites enables persistent infection in the untreated host. This translational update describes the host innate and adaptive immune responses in syphilis and the sophisticated mechanisms employed by T. pallidum to avoid immune clearance. Recent advances in immune profiling have enhanced our understanding of the host immune response and identified potential biomarkers for disease staging and treatment monitoring. However, knowledge gaps remain regarding T. pallidum's immune evasion mechanisms, the dynamics of cellular and humoral immunity, and the characteristics of long-term protective immune responses against T. pallidum. Bridging these gaps by integrating microbiology, immunology, and multiomics approaches is crucial for advancing diagnostic tools, therapeutic strategies, and vaccine development to ultimately reduce the global burden of syphilis.