Fig. 7. Mechanisms of pyroptosis, NETosis, and necroptosis.

A Pyroptosis is characterized by cell swelling, plasma membrane rupture, and the release of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18. Pyroptosis is triggered by the activation of inflammasomes, cytoplasmic complexes that sense danger signals, and initiate a caspase-1-dependent cascade that ultimately leads to cell death. B NETosis is a process in which neutrophils release DNA fibers coated with antimicrobial peptides to trap and kill pathogens. During NETosis, neutrophils undergo marked morphological changes, including chromatin decondensation, nuclear envelope rupture, and granule mixing, leading to the formation of neutrophil extracellular traps (NETs). The release of NETs is triggered by various stimuli, such as pathogens, cytokines, and immune complexes. C Necroptosis is mediated by death receptors. Upon activation of death receptors, such as TNFR1, receptor-interacting protein kinase 1 (RIPK1) binds to RIPK3 to form a necrosome. The necrosome complex promotes the oligomerization and phosphorylation of the mixed lineage kinase domain-like protein (MLKL). The oligomeric form of MLKL is translocated from the cytosol to the plasma membrane, leading to the formation of membrane pores and subsequent plasma membrane rupture. This results in the release of damage-associated molecular patterns (DAMPs), which trigger inflammation.