TLR4 and Sepsis: Su et al. demonstrated that platelet pyroptosis fostered inflammation and multi-organ damage in CLP-induced sepsis using platelet-specific GSDMD knockout mice.363 Pyroptotic platelets may release oxidized mitochondrial DNA (ox-mtDNA), which promotes NET formation, exacerbating platelet pyroptosis through the release of S100A8/A9 that targeted toll-like receptor 4 (TLR4), creating a self-amplifying cycle that results in excessive cytokines release.