Programmed cell death as a defence against infection

Key Points Pyroptosis is programmed lytic cell death caused by the cleavage of gasdermin D by caspases 1, 4, 5 and 11. Recent work suggests that pyroptosis defends against infection by vacuolar or cytosol-invasive bacteria. Necroptosis is programmed lytic cell death caused by RIPK3 activation of MLKL. Recent work has suggested that necroptosis defends against viral infection. Apoptosis can be activated by extrinsic and intrinsic signals. It is a crucial host defence mechanism, and pathogens have evolved to both evade and co-opt apoptosis. Apoptosis and necroptosis guard each other to make it difficult for pathogens to inhibit these programmed cell death mechanisms. Despite this, pathogens, such as mouse cytomegalovirus, seem to inhibit both pathways simultaneously. The signalling cascades that lead to apoptosis, necroptosis and pyroptosis have numerous interactions, creating a complex web of programmed cell death mechanisms to defend against infection. In this regard, physiological relevance for apoptosis and necroptotic cross guarding is established, but most other interactions remain to be fully explored. Neutrophil extracellular traps (NETs) and pore-induced intracellular traps (PITs) are mechanism to physically retain bacteria in the extracellular or the intracellular space, respectively. These cellular corpses can be considered as structures that exist in parallel to apoptotic bodies (the corpse of an apoptotic cell).