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Macrophage reprogramming by negatively charged membrane phospholipids controls infection

David M Cauvi1, Dennis Hawisher1, Paulo R Dores-Silva1

  • 1Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California, USA; and.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 17, 2018
PubMed

Insights

Negatively charged membrane phospholipids, like phosphatidylserine (PS), can reprogram macrophages to activate innate immunity. This phospholipid-driven immune response effectively controls infections by triggering neutrophil infiltration.

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.
Keywords:
extracellular vesiclesinflammationphosphatidylserinesepsis

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