Key Points
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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.
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Necroptosis is programmed lytic cell death caused by RIPK3 activation of MLKL. Recent work has suggested that necroptosis defends against viral infection.
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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.
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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.
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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.
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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).
Abstract
Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary 'arms race' with pathogens. Finally, we describe how the resulting cell corpses — apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) — promote the clearance of infection.
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Acknowledgements
E.A.M.'s laboratory is supported by US National Institutes of Health (NIH) grants AI097518 and AI119073, and the Yang Biomedical Scholars Award.
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Supplementary information S1 (table)
Inflammasome survival studies in Casp1−/−Casp11−/− or related mice (PDF 231 kb)
Glossary
- Apoptosis
-
A common form of cell death. Many physiological and developmental stimuli cause apoptosis, and this mechanism is frequently used to delete unwanted, superfluous or potentially harmful cells, such as those undergoing transformation.
- Necroptosis
-
Programmed lytic cell death via RIPK3 activation of MLKL.
- Pyroptosis
-
Programmed lytic cell death via cleavage of gasdermin D by caspases 1, 4, 5 and 11, and recently expanded to include lytic cell death caused by other gasdermin family proteins.
- Neutrophil extracellular traps
-
(NETs). Structures that form after NETosis.
- NETosis
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Programmed neutrophil death that results in formation of neutrophil extracellular traps (NETs).
- Apoptotic bodies
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Cellular corpses that form after apoptosis.
- Pore-induced intracellular traps
-
(PITs). Structures that form after pyroptosis and necroptosis to retain organelles and bacteria.
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Jorgensen, I., Rayamajhi, M. & Miao, E. Programmed cell death as a defence against infection. Nat Rev Immunol 17, 151–164 (2017). https://doi.org/10.1038/nri.2016.147
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DOI: https://doi.org/10.1038/nri.2016.147
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