Lipid asymmetry disruption by XKR8 orchestrates neutrophil extracellular trap formation and inhibits fungal infection - PubMed
3 hours ago
- #Antifungal immunity
- #Neutrophil extracellular traps
- #XKR8
- Neutrophil extracellular traps (NETs) are crucial for antimicrobial defense and various physiological processes.
- XKR8, a plasma membrane phospholipid scramblase, is identified as a key regulator of NET formation.
- XKR8 is cleaved by caspase-3 during NET induction, disrupting plasma membrane lipid asymmetry.
- Mutation of the caspase-3 cleavage site in XKR8 impairs NET formation.
- Calcium signals before lipid scrambling are essential for NET formation, but not after scrambling.
- Cleaved XKR8 alters membrane lipid tension and promotes Ca2+ signals via mechanosensitive channels.
- XKR8-deficient mice show compromised NET formation and impaired control of Candida albicans infection.
- The caspase-3-XKR8-phospholipid scrambling mechanism is central to NET formation and antifungal immunity.