trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• The role of mechanical forces in regulating polymorphonuclear leukocyte (PMN) function during migration across endothelial barriers is not fully understood.
• Understanding this process is critical for developing strategies against bacterial infections.

Purpose of the Study:

• To investigate the role of the mechanosensor Piezo1 in PMN function during trans-endothelial migration.
• To elucidate the molecular mechanisms by which mechanical forces regulate PMN bactericidal activity.

Main Methods:

• Genetic deletion of Piezo1 in PMNs.
• In vivo infection models (Pseudomonas aeruginosa).
• Microfluidic systems to apply defined mechanical forces.
• Calcium imaging and measurement of bactericidal function.

Main Results:

• Piezo1 in PMNs senses mechanical forces during trans-endothelial migration, inducing calcium signals.
• PMNs lacking Piezo1 exhibit impaired bacterial clearance and increased susceptibility to infection.
• Activating Piezo1 or applying mechanical forces enhances PMN bactericidal activity.
• Piezo1 upregulates NADPH oxidase 4, a key enzyme for bacterial killing.

Conclusions:

• Piezo1-mediated mechanosensing of PMN tension during endothelial transmigration is a critical host-defense mechanism.
• This pathway enhances PMN bactericidal function, crucial for controlling bacterial infections.