Treponema pallidum Protein TpF1 Inhibits Migration by Impairing Actin Polymerization via Toll-Like Receptor 4/PI3K/AKT in Microglia.

Abstract

Treponema pallidum induces a host immune response during central nervous system (CNS) invasion, prompting microglia to migrate to the site of injury, where they release effector molecules or phagocytose pathogens. However, the role of impaired microglial migration in the pathogenesis of T. pallidum infection remains poorly understood. In this study, we sought to explore the molecular mechanisms by which the T. pallidum protein TpF1 inhibits microglial migration. Microglial HMC3 cells were used to assess the effects of TpF1 on cellular migration and its impact on actin polymerization. Our findings demonstrate that TpF1 significantly reduces microglial migration in both horizontal and vertical directions. This effect correlates with a marked decrease in the filamentous actin (F-actin)/globular actin (G-actin) ratio, as confirmed by immunofluorescence analysis, which revealed a considerable reduction in F-actin levels. Moreover, TpF1 was found to suppress the expression of Toll-like receptor 4 (TLR4), phosphorylated PI3K (P-PI3K)/PI3K, phosphorylated AKT (P-AKT)/AKT, and Rac1. Inhibition of the TLR4/PI3K/AKT signaling pathway further impaired actin polymerization and migration. Collectively, our study identifies a novel mechanism by which TpF1 disrupts microglial migration via the TLR4/PI3K/AKT pathway, providing valuable insights into immune evasion strategies during T. pallidum-induced CNS infection.