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Author Spotlight: Advancing Syphilis Research — Innovations in Treponema pallidum Cultivation and Genetic Engineering
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Author Spotlight: Advancing Syphilis Research — Innovations in Treponema pallidum Cultivation and Genetic Engineering

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Treponema pallidum enhances human monocyte migration and invasion by dysregulating the MMP/TIMP balance

Shu-Wen Lin1, Zheng-Xiang Gao2, Li-Rong Lin1

  • 1Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.

International Immunopharmacology
|July 19, 2019
PubMed

Insights

Treponema pallidum, the syphilis bacterium, drives monocyte migration by altering matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinases (TIMP) balance, activating MAPK and NF-κB pathways.

Area of Science:

  • Pathogen-host interactions
  • Cellular and Molecular Biology
  • Immunology

Background:

  • Syphilis pathogenesis involves monocyte infiltration into lesions.
  • The role of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinases (TIMP) imbalance in Treponema pallidum (T. pallidum)-induced monocyte migration is poorly understood.

Purpose of the Study:

  • To investigate the influence of T. pallidum on THP-1 cell migration and invasion.
  • To explore changes in the MMP/TIMP balance and the involvement of MAPK and NF-κB signaling pathways.

Main Methods:

  • Evaluation of THP-1 cell migration and invasion.
  • Analysis of MMP-1, MMP-9, TIMP-1, and TIMP-2 mRNA and protein expression.
  • Assessment of MMP/TIMP ratios.
  • Inhibition studies targeting JNK, MEK/ERK, p38 MAPK, and NF-κB signaling pathways.

Main Results:

  • T. pallidum induced THP-1 cell migration and invasion.
  • Upregulation of MMP-1, MMP-9, and TIMP-1 expression; downregulation of TIMP-2 mRNA.
  • Increased MMP/TIMP ratios (MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-9/TIMP-1, MMP-9/TIMP-2).
  • Inhibition of MAPK and NF-κB pathways reduced MMP/TIMP ratios and suppressed cell migration/invasion.

Conclusions:

  • T. pallidum-induced MMP/TIMP imbalance enhances THP-1 cell migration and invasion.
  • MAPK and NF-κB signaling pathways are crucial in mediating this process.
  • This study reveals a novel mechanism in syphilis pathophysiology.
Keywords:
InvasionMMP/TIMP imbalanceMigrationMonocyteTreponema pallidum

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