Pyroptosis

Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.^[1]

The process is initiated by formation of a large supramolecular complex termed the inflammasome (also known as a pyroptosome) upon intracellular danger signals.^[2] The inflammasome activates a different set of caspases as compared to apoptosis, for example, caspase-1/4/5 in humans and caspase-11 in mice.^[3] These caspases contribute to the maturation and activation of the pro-inflammatory cytokines IL-1β and IL-18, as well as the pore-forming protein gasdermin D. Formation of pores causes cell membrane rupture and release of cytokines, as well as various damage-associated molecular pattern (DAMP) molecules such as HMGB-1, ATP and DNA, out of the cell. These molecules recruit more immune cells and further perpetuate the inflammatory cascade in the tissue.^[4]^[5]

However, in pathogenic chronic diseases, the inflammatory response does not eradicate the primary stimulus. A chronic form of inflammation ensues that ultimately contributes to tissue damage. Pyroptosis is associated with diseases including autoinflammatory, metabolic, and cardiovascular diseases, as well as cancer and neurodegeneration. Some examples of pyroptosis include the cell death induced in Salmonella-infected macrophages and abortively HIV-infected T helper cells.^[6]^[7]^[8]

^ Jorgensen I, Miao EA (May 2015). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews. 265 (1): 130–42. doi:10.1111/imr.12287. PMC 4400865. PMID 25879289.
^ Nirmala JG, Lopus M (April 2020). "Cell death mechanisms in eukaryotes". Cell Biology and Toxicology. 36 (2): 145–164. doi:10.1007/s10565-019-09496-2. PMID 31820165. S2CID 208869679.
^ Gong W, Shi Y, Ren J (March 2020). "Research progresses of molecular mechanism of pyroptosis and its related diseases". Immunobiology. 225 (2): 151884. doi:10.1016/j.imbio.2019.11.019. PMID 31822435. S2CID 209314359.
^ Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, et al. (August 2014). "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response". Nature Immunology. 15 (8): 738–48. doi:10.1038/ni.2919. PMID 24952504. S2CID 6928042.
^ Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al. (August 2014). "The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation". Nature Immunology. 15 (8): 727–37. doi:10.1038/ni.2913. PMC 4116676. PMID 24952505.
^ Fink SL, Cookson BT (November 2006). "Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages". Cellular Microbiology. 8 (11): 1812–25. doi:10.1111/j.1462-5822.2006.00751.x. PMID 16824040.
^ Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. (January 2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–14. Bibcode:2014Natur.505..509D. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.
^ Doitsh G, Greene WC (March 2016). "Dissecting How CD4 T Cells Are Lost During HIV Infection". Cell Host & Microbe. 19 (3): 280–91. doi:10.1016/j.chom.2016.02.012. PMC 4835240. PMID 26962940.

[pyro1-1] Jorgensen I, Miao EA (May 2015). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews. 265 (1): 130–42. doi:10.1111/imr.12287. PMC 4400865. PMID 25879289.

[pmid31820165-2] Nirmala JG, Lopus M (April 2020). "Cell death mechanisms in eukaryotes". Cell Biology and Toxicology. 36 (2): 145–164. doi:10.1007/s10565-019-09496-2. PMID 31820165. S2CID 208869679.

[Gong-3] Gong W, Shi Y, Ren J (March 2020). "Research progresses of molecular mechanism of pyroptosis and its related diseases". Immunobiology. 225 (2): 151884. doi:10.1016/j.imbio.2019.11.019. PMID 31822435. S2CID 209314359.

[4] Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, et al. (August 2014). "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response". Nature Immunology. 15 (8): 738–48. doi:10.1038/ni.2919. PMID 24952504. S2CID 6928042.

[5] Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al. (August 2014). "The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation". Nature Immunology. 15 (8): 727–37. doi:10.1038/ni.2913. PMC 4116676. PMID 24952505.

[Fink_2006-6] Fink SL, Cookson BT (November 2006). "Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages". Cellular Microbiology. 8 (11): 1812–25. doi:10.1111/j.1462-5822.2006.00751.x. PMID 16824040.

[Doitsh_2014-7] Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. (January 2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–14. Bibcode:2014Natur.505..509D. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.

[8] Doitsh G, Greene WC (March 2016). "Dissecting How CD4 T Cells Are Lost During HIV Infection". Cell Host & Microbe. 19 (3): 280–91. doi:10.1016/j.chom.2016.02.012. PMC 4835240. PMID 26962940.

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