Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion, and Migration in THP-1 Cells

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Monocyte-endothelial cell interactions are crucial for inflammatory responses, involving chemoattraction, adhesion, and migration.
• While selectins, integrins, and adhesion molecules are well-studied, the role of Toll-like receptor 2 (TLR2) in monocyte adhesion and migration requires further elucidation.

Purpose of the Study:

• To investigate the role of Toll-like receptor 2 (TLR2) in monocyte adhesion, endothelial barrier disruption, and migration.

Main Methods:

• Functional cell-based assays using wild type (WT), TLR2 knock-out (KO), and TLR2 knock-in (KI) THP-1 cells.
• Quantitative mass spectrometry, STRING protein analysis, and RT-qPCR were employed to identify associated proteins.

Main Results:

• TLR2 significantly promotes faster and stronger monocyte adhesion to the endothelium.
• TLR2 enhances endothelial barrier disruption upon endothelial activation and influences actin polymerization.
• Novel proteins associated with TLR2 function in monocyte adhesion and migration were identified.

Conclusions:

• Unstimulated TLR2 plays a significant role in modulating monocyte adhesion, endothelial barrier disruption, cell migration, and actin polymerization.
• TLR2's influence extends beyond pathogen sensing to actively regulate key steps in the inflammatory cell trafficking cascade.