Macrophage reprogramming by negatively charged membrane phospholipids controls infection.

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Extracellular vesicles (ECVs) mediate intercellular communication via lipid and nucleic acid transfer.
• The role of ECV phospholipids in cellular activation is understudied compared to proteins and microRNAs.
• Phosphatidylserine (PS) and phosphatidylcholine (PC) are abundant phospholipids in ECVs.

Purpose of the Study:

• To investigate the biological effects of phosphatidylserine (PS) and phosphatidylcholine (PC) on cellular activation.
• To determine the impact of these phospholipids on innate immune responses and infection control.

Main Methods:

• Exposure of peritoneal macrophages to phosphatidylserine (PS) and phosphatidylcholine (PC) liposomes in vivo.
• Transcriptomic analysis to assess gene expression changes.
• Evaluation of neutrophil infiltration and infection neutralization.

Main Results:

• PS and PC liposome treatment significantly modified gene expression in macrophages (approx. 4700 genes).
• PS liposome treatment upregulated chemokines and cytokines, leading to massive neutrophil infiltration.
• Both L- and D-stereoisomers of PS induced similar responses, indicating the effect relates to negative charge.

Conclusions:

• Increased negative charge within cells can trigger signaling cascades activating innate immune responses.
• Phosphatidylserine-mediated macrophage reprogramming enhances the innate immune system's ability to control infection.
• Membrane phospholipid charge plays a critical role in modulating immune cell function and host defense.