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Molecular Mechanisms of Pyroptosis

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Pyroptosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2641))

Abstract

Pyroptosis is a regulated form of cell death that leads to inflammation and plays a role in many different diseases. Pyroptosis was initially defined by the dependence on caspase-1, a protease which is activated by innate immune signaling complexes called inflammasomes. Caspase-1 cleaves the protein gasdermin D, releasing the N-terminal pore-forming domain, which inserts into the plasma membrane. Recent studies have revealed that other gasdermin family members form plasma membrane pores, leading to lytic cell death, and the definition of pyroptosis was revised to gasdermin-dependent cell death. In this review, we discuss how the use of the term pyroptosis has changed over time, as well as currently understood molecular mechanisms leading to pyroptosis and functional consequences of this form of regulated cell death.

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References

  1. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257. https://doi.org/10.1038/bjc.1972.33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73(4):1907–1916. https://doi.org/10.1128/IAI.73.4.1907-1916.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Julien O, Wells JA (2017) Caspases and their substrates. Cell Death Differ 24(8):1380–1389. https://doi.org/10.1038/cdd.2017.44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cookson BT, Brennan MA (2001) Pro-inflammatory programmed cell death. Trends Microbiol 9(3):113–114. https://doi.org/10.1016/s0966-842x(00)01936-3

    Article  CAS  PubMed  Google Scholar 

  6. Fink SL, Bergsbaken T, Cookson BT (2008) Anthrax lethal toxin and salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci U S A 105(11):4312–4317. https://doi.org/10.1073/pnas.0707370105

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fantuzzi G, Dinarello CA (1999) Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J Clin Immunol 19(1):1–11. https://doi.org/10.1023/a:1020506300324

    Article  CAS  PubMed  Google Scholar 

  8. Fink SL, Cookson BT (2006) Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8(11):1812–1825. https://doi.org/10.1111/j.1462-5822.2006.00751.x

    Article  PubMed  Google Scholar 

  9. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660–665. https://doi.org/10.1038/nature15514

    Article  CAS  PubMed  Google Scholar 

  10. He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res 25(12):1285–1298. https://doi.org/10.1038/cr.2015.139

    Article�� CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J (2016) Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535(7610):153–158. https://doi.org/10.1038/nature18629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC, Shao F (2016) Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535(7610):111–116. https://doi.org/10.1038/nature18590

    Article  CAS  PubMed  Google Scholar 

  13. Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526(7575):666–671. https://doi.org/10.1038/nature15541

    Article  CAS  PubMed  Google Scholar 

  14. Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM (2011) Non-canonical inflammasome activation targets caspase-11. Nature 479(7371):117–121. https://doi.org/10.1038/nature10558

    Article  CAS  PubMed  Google Scholar 

  15. Orning P, Weng D, Starheim K, Ratner D, Best Z, Lee B, Brooks A, Xia S, Wu H, Kelliher MA, Berger SB, Gough PJ, Bertin J, Proulx MM, Goguen JD, Kayagaki N, Fitzgerald KA, Lien E (2018) Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362(6418):1064–1069. https://doi.org/10.1126/science.aau2818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sarhan J, Liu BC, Muendlein HI, Li P, Nilson R, Tang AY, Rongvaux A, Bunnell SC, Shao F, Green DR, Poltorak A (2018) Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proc Natl Acad Sci U S A 115(46):E10888–E10897. https://doi.org/10.1073/pnas.1809548115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Burgener SS, Leborgne NGF, Snipas SJ, Salvesen GS, Bird PI, Benarafa C (2019) Cathepsin G inhibition by Serpinb1 and Serpinb6 prevents programmed necrosis in neutrophils and monocytes and reduces GSDMD-driven inflammation. Cell Rep 27(12):3646–3656. https://doi.org/10.1016/j.celrep.2019.05.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kambara H, Liu F, Zhang X, Liu P, Bajrami B, Teng Y, Zhao L, Zhou S, Yu H, Zhou W, Silberstein LE, Cheng T, Han M, Xu Y, Luo HR (2018) Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death. Cell Rep 22(11):2924–2936. https://doi.org/10.1016/j.celrep.2018.02.067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kovacs SB, Miao EA (2017) Gasdermins: effectors of Pyroptosis. Trends Cell Biol 27(9):673–684. https://doi.org/10.1016/j.tcb.2017.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, Wang K, Shao F (2017) Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547(7661):99–103. https://doi.org/10.1038/nature22393

    Article  CAS  PubMed  Google Scholar 

  21. Shi J, Gao W, Shao F (2017) Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 42(4):245–254. https://doi.org/10.1016/j.tibs.2016.10.004

    Article  CAS  PubMed  Google Scholar 

  22. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D’Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jaattela M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G, Marine JC, Martin SJ, Martinou JC, Medema JP, Mehlen P, Meier P, Melino S, Miao EA, Molkentin JD, Moll UM, Munoz-Pinedo C, Nagata S, Nunez G, Oberst A, Oren M, Overholtzer M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pereira DM, Pervaiz S, Peter ME, Piacentini M, Pinton P, Prehn JHM, Puthalakath H, Rabinovich GA, Rehm M, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Ryan KM, Sayan E, Scorrano L, Shao F, Shi Y, Silke J, Simon HU, Sistigu A, Stockwell BR, Strasser A, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Thorburn A, Tsujimoto Y, Turk B, Vanden Berghe T, Vandenabeele P, Vander Heiden MG, Villunger A, Virgin HW, Vousden KH, Vucic D, Wagner EF, Walczak H, Wallach D, Wang Y, Wells JA, Wood W, Yuan J, Zakeri Z, Zhivotovsky B, Zitvogel L, Melino G, Kroemer G (2018) Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ 25(3):486–541. https://doi.org/10.1038/s41418-017-0012-4

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zheng D, Liwinski T, Elinav E (2020) Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov 6:36. https://doi.org/10.1038/s41421-020-0167-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liang F, Zhang F, Zhang L, Wei W (2020) The advances in pyroptosis initiated by inflammasome in inflammatory and immune diseases. Inflamm Res 69(2):159–166. https://doi.org/10.1007/s00011-020-01315-3

    Article  CAS  PubMed  Google Scholar 

  25. Swanson KV, Deng M, Ting JP (2019) The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 19(8):477–489. https://doi.org/10.1038/s41577-019-0165-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bertheloot D, Latz E, Franklin BS (2021) Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18(5):1106–1121. https://doi.org/10.1038/s41423-020-00630-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zangiabadi S, Abdul-Sater AA (2022) Regulation of the NLRP3 Inflammasome by posttranslational modifications. J Immunol 208(2):286–292. https://doi.org/10.4049/jimmunol.2100734

    Article  CAS  PubMed  Google Scholar 

  28. Zhao C, Zhao W (2020) NLRP3 Inflammasome-a key player in antiviral responses. Front Immunol 11:211. https://doi.org/10.3389/fimmu.2020.00211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang C, Yang T, Xiao J, Xu C, Alippe Y, Sun K, Kanneganti TD, Monahan JB, Abu-Amer Y, Lieberman J, Mbalaviele G (2021) NLRP3 inflammasome activation triggers gasdermin D-independent inflammation. Sci Immunol 6(64):eabj3859. https://doi.org/10.1126/sciimmunol.abj3859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Duncan JA, Canna SW (2018) The NLRC4 Inflammasome. Immunol Rev 281(1):115–123. https://doi.org/10.1111/imr.12607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Naseer N, Egan MS, Reyes Ruiz VM, Scott WP, Hunter EN, Demissie T, Rauch I, Brodsky IE, Shin S (2022) Human NAIP/NLRC4 and NLRP3 inflammasomes detect salmonella type III secretion system activities to restrict intracellular bacterial replication. PLoS Pathog 18(1):e1009718. https://doi.org/10.1371/journal.ppat.1009718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sundaram B, Kanneganti TD (2021) Advances in understanding activation and function of the NLRC4 Inflammasome. Int J Mol Sci 22(3). https://doi.org/10.3390/ijms22031048

  33. Mitchell PS, Sandstrom A, Vance RE (2019) The NLRP1 inflammasome: new mechanistic insights and unresolved mysteries. Curr Opin Immunol 60:37–45. https://doi.org/10.1016/j.coi.2019.04.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bauernfried S, Hornung V (2022) Human NLRP1: from the shadows to center stage. J Exp Med 219(1). https://doi.org/10.1084/jem.20211405

  35. Taabazuing CY, Griswold AR, Bachovchin DA (2020) The NLRP1 and CARD8 inflammasomes. Immunol Rev 297(1):13–25. https://doi.org/10.1111/imr.12884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Griswold AR, Huang HC, Bachovchin DA (2022) The NLRP1 Inflammasome induces Pyroptosis in human corneal epithelial cells. Invest Ophthalmol Vis Sci 63(3):2. https://doi.org/10.1167/iovs.63.3.2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kumari P, Russo AJ, Shivcharan S, Rathinam VA (2020) AIM2 in health and disease: Inflammasome and beyond. Immunol Rev 297(1):83–95. https://doi.org/10.1111/imr.12903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lammert CR, Frost EL, Bellinger CE, Bolte AC, McKee CA, Hurt ME, Paysour MJ, Ennerfelt HE, Lukens JR (2020) AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment. Nature 580(7805):647–652. https://doi.org/10.1038/s41586-020-2174-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sharma D, Malik A, Balakrishnan A, Malireddi RKS, Kanneganti TD (2020) RIPK3 promotes Mefv expression and pyrin Inflammasome activation via modulation of mTOR signaling. J Immunol 205(10):2778–2785. https://doi.org/10.4049/jimmunol.2000244

    Article  CAS  PubMed  Google Scholar 

  40. Schnappauf O, Chae JJ, Kastner DL, Aksentijevich I (2019) The pyrin Inflammasome in health and disease. Front Immunol 10:1745. https://doi.org/10.3389/fimmu.2019.01745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Magnotti F, Lefeuvre L, Benezech S, Malsot T, Waeckel L, Martin A, Kerever S, Chirita D, Desjonqueres M, Duquesne A, Gerfaud-Valentin M, Laurent A, Seve P, Popoff MR, Walzer T, Belot A, Jamilloux Y, Henry T (2019) Pyrin dephosphorylation is sufficient to trigger inflammasome activation in familial Mediterranean fever patients. EMBO Mol Med 11(11):e10547. https://doi.org/10.15252/emmm.201910547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Agnew A, Nulty C, Creagh EM (2021) Regulation, activation and function of Caspase-11 during health and disease. Int J Mol Sci 22(4). https://doi.org/10.3390/ijms22041506

  43. Hagar JA, Powell DA, Aachoui Y, Ernst RK, Miao EA (2013) Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock. Science 341(6151):1250–1253. https://doi.org/10.1126/science.1240988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszynski A, Forsberg LS, Carlson RW, Dixit VM (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341(6151):1246–1249. https://doi.org/10.1126/science.1240248

    Article  CAS  PubMed  Google Scholar 

  45. Matikainen S, Nyman TA, Cypryk W (2020) Function and regulation of noncanonical Caspase-4/5/11 Inflammasome. J Immunol 204(12):3063–3069. https://doi.org/10.4049/jimmunol.2000373

    Article  CAS  PubMed  Google Scholar 

  46. Smith AP, Creagh EM (2022) Caspase-4 and -5 biology in the pathogenesis of inflammatory bowel disease. Front Pharmacol 13:919567. https://doi.org/10.3389/fphar.2022.919567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lara-Reyna S, Caseley EA, Topping J, Rodrigues F, Jimenez Macias J, Lawler SE, McDermott MF (2022) Inflammasome activation: from molecular mechanisms to autoinflammation. Clin Transl Immunology 11(7):e1404. https://doi.org/10.1002/cti2.1404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Angosto-Bazarra D, Molina-Lopez C, Pelegrin P (2022) Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles. Commun Biol 5(1):524. https://doi.org/10.1038/s42003-022-03491-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Venuprasad K, Theiss AL (2021) NLRP6 in host defense and intestinal inflammation. Cell Rep 35(4):109043. https://doi.org/10.1016/j.celrep.2021.109043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Carriere J, Dorfleutner A, Stehlik C (2021) NLRP7: from inflammasome regulation to human disease. Immunology 163(4):363–376. https://doi.org/10.1111/imm.13372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dell’Oste V, Gatti D, Giorgio AG, Gariglio M, Landolfo S, De Andrea M (2015) The interferon-inducible DNA-sensor protein IFI16: a key player in the antiviral response. New Microbiol 38(1):5–20

    PubMed  Google Scholar 

  52. Garlanda C, Dinarello CA, Mantovani A (2013) The interleukin-1 family: back to the future. Immunity 39(6):1003–1018. https://doi.org/10.1016/j.immuni.2013.11.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Nakanishi K (2018) Unique action of Interleukin-18 on T cells and other immune cells. Front Immunol 9:763. https://doi.org/10.3389/fimmu.2018.00763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Evavold CL, Kagan JC (2022) Diverse control mechanisms of the Interleukin-1 cytokine family. Front Cell Dev Biol 10:910983. https://doi.org/10.3389/fcell.2022.910983

    Article  PubMed  PubMed Central  Google Scholar 

  55. Xia S, Zhang Z, Magupalli VG, Pablo JL, Dong Y, Vora SM, Wang L, Fu TM, Jacobson MP, Greka A, Lieberman J, Ruan J, Wu H (2021) Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 593(7860):607–611. https://doi.org/10.1038/s41586-021-03478-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bergsbaken T, Fink SL, den Hartigh AB, Loomis WP, Cookson BT (2011) Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation. J Immunol 187(5):2748–2754. https://doi.org/10.4049/jimmunol.1100477

    Article  CAS  PubMed  Google Scholar 

  57. Ruhl S, Shkarina K, Demarco B, Heilig R, Santos JC, Broz P (2018) ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science 362(6417):956–960. https://doi.org/10.1126/science.aar7607

    Article  CAS  PubMed  Google Scholar 

  58. Santa Cruz Garcia AB, Schnur KP, Malik AB, Mo GCH (2022) Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry. Nat Commun 13(1):52. https://doi.org/10.1038/s41467-021-27692-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. von Moltke J, Trinidad NJ, Moayeri M, Kintzer AF, Wang SB, van Rooijen N, Brown CR, Krantz BA, Leppla SH, Gronert K, Vance RE (2012) Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature 490(7418):107–111. https://doi.org/10.1038/nature11351

    Article  CAS  Google Scholar 

  60. Davis MA, Fairgrieve MR, Den Hartigh A, Yakovenko O, Duvvuri B, Lood C, Thomas WE, Fink SL, Gale M Jr (2019) Calpain drives pyroptotic vimentin cleavage, intermediate filament loss, and cell rupture that mediates immunostimulation. Proc Natl Acad Sci U S A 116(11):5061–5070. https://doi.org/10.1073/pnas.1818598116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib MR, Kinoshita T, Suda T (2021) Gasdermin D mediates the maturation and release of IL-1alpha downstream of inflammasomes. Cell Rep 34(12):108887. https://doi.org/10.1016/j.celrep.2021.108887

    Article  CAS  PubMed  Google Scholar 

  62. Gross O, Yazdi AS, Thomas CJ, Masin M, Heinz LX, Guarda G, Quadroni M, Drexler SK, Tschopp J (2012) Inflammasome activators induce interleukin-1alpha secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36(3):388–400. https://doi.org/10.1016/j.immuni.2012.01.018

    Article  CAS  PubMed  Google Scholar 

  63. Kayagaki N, Kornfeld OS, Lee BL, Stowe IB, O’Rourke K, Li Q, Sandoval W, Yan D, Kang J, Xu M, Zhang J, Lee WP, McKenzie BS, Ulas G, Payandeh J, Roose-Girma M, Modrusan Z, Reja R, Sagolla M, Webster JD, Cho V, Andrews TD, Morris LX, Miosge LA, Goodnow CC, Bertram EM, Dixit VM (2021) NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591(7848):131–136. https://doi.org/10.1038/s41586-021-03218-7

    Article  CAS  PubMed  Google Scholar 

  64. Yang H, Wang H, Andersson U (2020) Targeting inflammation driven by HMGB1. Front Immunol 11:484. https://doi.org/10.3389/fimmu.2020.00484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Stros M (2010) HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta 1799(1–2):101–113. https://doi.org/10.1016/j.bbagrm.2009.09.008

    Article  CAS  PubMed  Google Scholar 

  66. Wu C, Lu W, Zhang Y, Zhang G, Shi X, Hisada Y, Grover SP, Zhang X, Li L, Xiang B, Shi J, Li XA, Daugherty A, Smyth SS, Kirchhofer D, Shiroishi T, Shao F, Mackman N, Wei Y, Li Z (2019) Inflammasome activation triggers blood clotting and host death through Pyroptosis. Immunity 50(6):1401–1411. e1404. https://doi.org/10.1016/j.immuni.2019.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pawlinski R, Mackman N (2010) Cellular sources of tissue factor in endotoxemia and sepsis. Thromb Res 125(Suppl 1):S70–S73. https://doi.org/10.1016/j.thromres.2010.01.042

    Article  CAS  PubMed  Google Scholar 

  68. Brennan MA, Cookson BT (2000) Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38(1):31–40. https://doi.org/10.1046/j.1365-2958.2000.02103.x

    Article  CAS  PubMed  Google Scholar 

  69. Loomis WP, den Hartigh AB, Cookson BT, Fink SL (2019) Diverse small molecules prevent macrophage lysis during pyroptosis. Cell Death Dis 10(4):326. https://doi.org/10.1038/s41419-019-1559-4

    Article  PubMed  PubMed Central  Google Scholar 

  70. Jorgensen I, Zhang Y, Krantz BA, Miao EA (2016) Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J Exp Med 213(10):2113–2128. https://doi.org/10.1084/jem.20151613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jorgensen I, Lopez JP, Laufer SA, Miao EA (2016) IL-1beta, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol 46(12):2761–2766. https://doi.org/10.1002/eji.201646647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nozaki K, Li L, Miao EA (2022) Innate sensors trigger regulated cell death to combat intracellular infection. Annu Rev Immunol 40:469–498. https://doi.org/10.1146/annurev-immunol-101320-011235

    Article  CAS  PubMed  Google Scholar 

  73. Bedoui S, Herold MJ, Strasser A (2020) Emerging connectivity of programmed cell death pathways and its physiological implications. Nat Rev Mol Cell Biol 21(11):678–695. https://doi.org/10.1038/s41580-020-0270-8

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Marisa J. Anderson, Andreas B. den Hartigh & Susan L. Fink

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  1. Marisa J. Anderson
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  2. Andreas B. den Hartigh
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  3. Susan L. Fink
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Correspondence to Susan L. Fink .

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    Susan L. Fink

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Anderson, M.J., den Hartigh, A.B., Fink, S.L. (2023). Molecular Mechanisms of Pyroptosis. In: Fink, S.L. (eds) Pyroptosis. Methods in Molecular Biology, vol 2641. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3040-2_1

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  • DOI: https://doi.org/10.1007/978-1-0716-3040-2_1

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3039-6

  • Online ISBN: 978-1-0716-3040-2

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