Treponema pallidum Protein TpF1 Inhibits Migration by Impairing Actin Polymerization via Toll-Like Receptor

Yuan-Yi Zhao1, Lin Xie1, Ruo-Ying Wang1

  • 1Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China.

PubMed

Insights

The Treponema pallidum protein TpF1 inhibits microglial migration by disrupting actin polymerization via the Toll-like receptor 4 (TLR4) pathway. This finding reveals a novel immune evasion mechanism in central nervous system (CNS) infections.

Area of Science:

  • Neuroimmunology
  • Infectious Diseases
  • Cell Biology

Background:

  • Treponema pallidum invades the central nervous system (CNS), triggering microglial responses.
  • Impaired microglial migration's role in T. pallidum pathogenesis is poorly understood.
  • Microglia are crucial immune cells in the CNS, involved in pathogen clearance and injury response.

Purpose of the Study:

  • To investigate the molecular mechanisms by which the T. pallidum protein TpF1 inhibits microglial migration.
  • To elucidate TpF1's impact on actin polymerization and related signaling pathways.
  • To understand T. pallidum's immune evasion strategies in the CNS.

Main Methods:

  • Utilized microglial HMC3 cells to assess TpF1's effects on migration and actin polymerization.
  • Quantified changes in filamentous actin (F-actin) and globular actin (G-actin) ratio using immunofluorescence.
  • Analyzed the expression of Toll-like receptor 4 (TLR4), PI3K/AKT pathway components, and Rac1.

Main Results:

  • TpF1 significantly reduced microglial migration in horizontal and vertical directions.
  • TpF1 decreased the F-actin/G-actin ratio, indicating impaired actin polymerization.
  • TpF1 suppressed TLR4, phosphorylated PI3K (P-PI3K)/PI3K, phosphorylated AKT (P-AKT)/AKT, and Rac1 expression.

Conclusions:

  • TpF1 disrupts microglial migration by inhibiting actin polymerization through the TLR4/PI3K/AKT signaling pathway.
  • This study identifies a novel mechanism of immune evasion by T. pallidum in the CNS.
  • Findings provide insights into the pathogenesis of T. pallidum-induced CNS infections.

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