Fig. 4

Pyroptosis, an inflammatory host response [134]. Caspase-1 is cleaved and activated in response to multiple stimuli, but once activated, caspase-1 results in a conserved program of cell death referred to as pyroptosis. Caspase-1 activation also leads to rapid formation of plasma-membrane pores with a diameter of 1.1–2.4 nm. These pores dissipate cellular ionic gradients, allowing water influx, cell swelling, and osmotic lysis. The pro-forms of interleukin-1β (IL-1β) and IL-18 are processed by caspase-1 and released during pyroptosis, although the exact mechanism of secretion remains controversial. Secretion does not require lysis and is temporally associated with caspase-1-dependent pore formation, suggesting that these pores facilitate cytokine release. Other suggested secretion mechanisms include caspase-1-independent lysosome exocytosis and microvesicle shedding. Caspase-1 activity results in cleavage of chromosomal DNA by an unidentified endonuclease. Cleavage of DNA does not result in the oligonucleosomal fragments observed during apoptosis. Nuclear condensation is also observed but nuclear integrity is maintained, unlike the nuclear fragmentation observed during apoptosis