A feedback loop between platelets and NETs amplifies inflammation in severe sepsis

Sepsis-derived S100A8/A9 induces GSDMD-dependent platelet pyroptosis via the TLR4-ROS-NLRP3-caspase 1 pathway, leading to the release of oxidized mitochondrial DNA that contributes to the formation of neutrophil extracellular traps (NETs). NETs in turn release S100A8/A9 and accelerate platelet pyroptosis, forming a positive feedback loop and thereby amplifying the production of proinflammatory cytokines.