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.
during pyroptosis. Pyroptosis, as a form of programmed cell death, has many morphological differences as compared to apoptosis. Both pyroptosis and apoptosis...
signals that lead to Pyroptosis by Caspase-1 are listed below: DNA in the host cytosol binds to AIM2-Like Receptors inducing Pyroptosis Type III secretion...
indicating pyroptosis may in fact be necessary for secretion in some way. Following the inflammatory response, an activated Caspase-1 can induce pyroptosis, a...
Sequential activation of these proteins leads to membrane permeabilization. Pyroptosis is a distinct type of regulated cell death, exhibiting a necrotic morphology...
allow the release of interleukin-1 (IL-1) family cytokines and drive pyroptosis. Several current studies have revealed that GSDMD serves as a specific...
oxaliplatin and bortezomib, or radiotherapy and photodynamic therapy (PDT). Pyroptosis is a highly inflammatory form of programmed cell death that occurs most...
Institutes of Health. Recent studies demonstrated that caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death, drives CD4 T-cell...
form of programmed cell death distinct from apoptosis, referred to as pyroptosis, which is responsible for the release of mature cytokines. Additionally...
induces pyroptosis. The advances contributed to firmly establishing the sequence of events leading from inflammasome activation to pyroptosis, DAMP release...
inside the cell and a programmed cell-death, known as pyroptosis, kills the infected cell. Pyroptosis is mediated via caspase-1 and is characterized by cell...
low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells...
cause the activation of other caspase proteins, leading to septic shock, pyroptosis, and often organismal death. LPS is a known activator of innate immune...
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