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Burn the house, save the day: pyroptosis in pathogen restriction

Dave Boucher
  • Corresponding author
  • Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kaiwen W. Chen
  • Corresponding author
  • Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kate Schroder
  • Corresponding author
  • Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-01-14 | DOI: https://doi.org/10.1515/infl-2015-0001


Many programmed cell death pathways are essential for organogenesis, development, immunity and the maintenance of homeostasis in multicellular organisms. Pyroptosis, a highly proinflammatory form of cell death, is a critical innate immune response to prevent intracellular infection. Pyroptosis is induced upon the activation of proinflammatory caspases within macromolecular signalling platforms called inflammasomes. This article reviews our understanding of pyroptosis induction, the function of inflammatory caspases in pyroptosis execution, and the importance of pyroptosis for pathogen clearance. It also highlights the situations in which extensive pyroptosis may in fact be detrimental to the host, leading to immune cell depletion or cytokine storm. Current efforts to understand the beneficial and pathological roles of pyroptosis bring the promise of new approaches to fight infectious diseases.

Keywords : pyroptosis; caspase; inflammasomes; pathogen control; immune evasion


  • [1] Lockshin, R. A., and C. M. William, Programmed Cell Death. 3. Neural Control of the Breakdown of the Intersegmental Muscles of Silkmoths, J. Insect. Physiol., 1965, 11, 601-610 Google Scholar

  • [2] Galluzzi, L., I. Vitale, J. M. Abrams, E. S. Alnemri, E. H. Baehrecke, M. V. Blagosklonny, T. M. Dawson, V. L. Dawson, W. S. El-Deiry, S. Fulda, et al., Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012, Cell Death Differ., 2012, 19, 107-120 Web of ScienceCrossrefGoogle Scholar

  • [3] Hagar, J. A., and E. A. Miao, Detection of cytosolic bacteria by inflammatory caspases, Curr. Opin. Microbiol., 2014, 17, 61-66 CrossrefWeb of ScienceGoogle Scholar

  • [4] Zychlinsky, A., M. C. Prevost, and P. J. Sansonetti, Shigella flexneri induces apoptosis in infected macrophages, Nature, 1992, 358, 167-169 Google Scholar

  • [5] Monack, D. M., B. Raupach, A. E. Hromockyj, and S. Falkow, Salmonella typhimurium invasion induces apoptosis in infected macrophages, Proc. Natl. Acad. Sci. U S A, 1996, 93, 9833-9838 Google Scholar

  • [6] Brennan, M. A., and B. T. Cookson, Salmonella induces macrophage death by caspase-1-dependent necrosis, Mol. Microbiol., 2000, 38, 31-40 Google Scholar

  • [7] Cookson, B. T., and M. A. Brennan, Pro-inflammatory programmed cell death, Trends Microbiol., 2001, 9, 113-114 CrossrefGoogle Scholar

  • [8] Fuentes-Prior, P., and G. S. Salvesen, The protein structures that shape caspase activity, specificity, activation and inhibition, Biochem. J., 2004, 384, 201-232 Google Scholar

  • [9] Schroder, K., and J. Tschopp, The inflammasomes, Cell, 2010, 140, 821-832 Web of ScienceGoogle Scholar

  • [10] Lamkanfi, M., and V. M. Dixit, Mechanisms and functions of inflammasomes, Cell, 2014, 157, 1013-1022 Google Scholar

  • [11] Martinon, F., K. Burns, and J. Tschopp, The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta, Mol. Cell, 2002, 10, 417-426 CrossrefGoogle Scholar

  • [12] Martinon, F., and J. Tschopp, Inflammatory caspases and inflammasomes: master switches of inflammation, Cell Death Differ., 2007, 14, 10-22 Web of ScienceCrossrefGoogle Scholar

  • [13] MacCorkle, R. A., K. W. Freeman, and D. M. Spencer, Synthetic activation of caspases: artificial death switches, Proc. Natl. Acad. Sci. U S A, 1998, 95, 3655-3660 Google Scholar

  • [14] Broz, P., J. von Moltke, J. W. Jones, R. E. Vance, and D. M. Monack, Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing, Cell Host Microbe, 2010, 8, 471-483 Web of ScienceGoogle Scholar

  • [15] Oberst, A., C. Pop, A. G. Tremblay, V. Blais, J. B. Denault, G. S. Salvesen, and D. R. Green, Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation, J. Biol. Chem., 2010, 285, 16632-16642 Google Scholar

  • [16] Chen, K. W., C. J. Gross, F. V. Sotomayor, K. J. Stacey, J. Tschopp, M. J. Sweet, and K. Schroder, The neutrophil NLRC4 inflammasome selectively promotes IL-1beta maturation without pyroptosis during acute Salmonella challenge, Cell Rep., 2014, 8, 570-582 Web of ScienceGoogle Scholar

  • [17] Kayagaki, N., M. T. Wong, I. B. Stowe, S. R. Ramani, L. C. Gonzalez, S. Akashi-Takamura, K. Miyake, J. Zhang, W. P. Lee, A. Muszynski, et al., Noncanonical inflammasome activation by intracellular LPS independent of TLR4, Science, 2013, 341, 1246-1249 Web of ScienceGoogle Scholar

  • [18] Hagar, J. A., D. A. Powell, Y. Aachoui, R. K. Ernst, and E. A. Miao, Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock, Science, 2013, 341, 1250-1253 Web of ScienceGoogle Scholar

  • [19] Rathinam, V. A., S. K. Vanaja, L. Waggoner, A. Sokolovska, C. Becker, L. M. Stuart, J. M. Leong, and K. A. Fitzgerald, TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria, Cell, 2012, 150, 606-619 Google Scholar

  • [20] Shi, J., Y. Zhao, Y. Wang, W. Gao, J. Ding, P. Li, L. Hu, and F. Shao, Inflammatory caspases are innate immune receptors for intracellular LPS, Nature, 2014, 514, 187-192 Web of ScienceGoogle Scholar

  • [21] Knodler, L. A., S. M. Crowley, H. P. Sham, H. Yang, M. Wrande, C. Ma, R. K. Ernst, O. Steele-Mortimer, J. Celli, and B. A. Vallance, Noncanonical inflammasome activation of caspase-4/ caspase-11 mediates epithelial defenses against enteric bacterial pathogens, Cell Host Microbe, 2014, 16, 249-256 Web of ScienceGoogle Scholar

  • [22] Kajiwara, Y., T. Schiff, G. Voloudakis, M. A. Gama Sosa, G. Elder, O. Bozdagi, and J. D. Buxbaum, A critical role for human caspase-4 in endotoxin sensitivity, J. Immunol., 2014, 193, 335-343 Web of ScienceGoogle Scholar

  • [23] Franchi, L., N. Kamada, Y. Nakamura, A. Burberry, P. Kuffa, S. Suzuki, M. H. Shaw, Y. G. Kim, and G. Nunez, NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense, Nat. Immunol., 2012, 13, 449-456 Web of ScienceGoogle Scholar

  • [24] Miao, E. A., I. A. Leaf, P. M. Treuting, D. P. Mao, M. Dors, A. Sarkar, S. E. Warren, M. D. Wewers, and A. Aderem, Caspase- 1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria, Nat. Immunol., 2010, 11, 1136-1142 Web of ScienceGoogle Scholar

  • [25] Raupach, B., S. K. Peuschel, D. M. Monack, and A. Zychlinsky, Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection, Infect. Immun., 2006, 74, 4922-4926 Google Scholar

  • [26] Oppenheim, J. J., P. Tewary, G. de la Rosa, and D. Yang, Alarmins initiate host defense, Adv. Exp. Med. Biol., 2007, 601, 185-194 Google Scholar

  • [27] Said-Sadier, N., and D. M. Ojcius, Alarmins, inflammasomes and immunity, Biomed. J., 2012, 35, 437-449 Google Scholar

  • [28] Moussion, C., N. Ortega, and J. P. Girard, The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’?, PLoS One, 2008, 3, e3331 Google Scholar

  • [29] Scaffidi, P., T. Misteli, and M. E. Bianchi, Release of chromatin protein HMGB1 by necrotic cells triggers inflammation, Nature, 2002, 418, 191-195 Web of ScienceGoogle Scholar

  • [30] Bergsbaken, T., S. L. Fink, and B. T. Cookson, Pyroptosis: host cell death and inflammation, Nat. Rev. Microbiol., 2009, 7, 99-109 Web of ScienceGoogle Scholar

  • [31] Franklin, B. S., L. Bossaller, D. De Nardo, J. M. Ratter, A. Stutz, G. Engels, C. Brenker, M. Nordhoff, S. R. Mirandola, A. Al-Amoudi, et al., The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation, Nat. Immunol., 2014, 15, 727-737 Web of ScienceGoogle Scholar

  • [32] Baroja-Mazo, A., F. Martin-Sanchez, A. I. Gomez, C. M. Martinez, J. Amores-Iniesta, V. Compan, M. Barbera- Cremades, J. Yague, E. Ruiz-Ortiz, J. Anton, et al., The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response, Nat. Immunol., 2014, 15, 738-748 Web of ScienceGoogle Scholar

  • [33] Bergsbaken, T., S. L. Fink, A. B. den Hartigh, W. P. Loomis, and B. T. Cookson, Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation, J. Immunol., 2011, 187, 2748-2754 Web of ScienceGoogle Scholar

  • [34] Mansour, S. C., O. M. Pena, and R. E. Hancock, Host defense peptides: front-line immunomodulators, Trends Immunol., 2014, 35, 443-450 Web of ScienceCrossrefGoogle Scholar

  • [35] Sellin, M. E., A. A. Muller, B. Felmy, T. Dolowschiak, M. Diard, A. Tardivel, K. M. Maslowski, and W. D. Hardt, Epitheliumintrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa, Cell Host Microbe, 2014, 16, 237-248 Web of ScienceGoogle Scholar

  • [36] LaRock, C. N., and B. T. Cookson, The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing, Cell Host Microbe, 2012, 12, 799-805 Web of ScienceCrossrefGoogle Scholar

  • [37] Kobayashi, T., M. Ogawa, T. Sanada, H. Mimuro, M. Kim, H. Ashida, R. Akakura, M. Yoshida, M. Kawalec, J. M. Reichhart, et al., The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection, Cell Host Microbe, 2013, 13, 570-583 Web of ScienceGoogle Scholar

  • [38] Upton, J. W., and F. K. Chan, Staying alive: cell death in antiviral immunity, Mol. Cell, 2014, 54, 273-280 Web of ScienceGoogle Scholar

  • [39] Lamkanfi, M., and V. M. Dixit, Modulation of inflammasome pathways by bacterial and viral pathogens, J. Immunol., 2011, 187, 597-602 Google Scholar

  • [40] Sagulenko, V., S. J. Thygesen, D. P. Sester, A. Idris, J. A. Cridland, P. R. Vajjhala, T. L. Roberts, K. Schroder, J. E. Vince, J. M. Hill, et al., AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC, Cell Death Differ., 2013, 20, 1149-1160 CrossrefWeb of ScienceGoogle Scholar

  • [41] Aachoui, Y., V. Sagulenko, E. A. Miao, and K. J. Stacey, Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection, Curr. Opin. Microbiol., 2013, 16, 319-326 CrossrefWeb of ScienceGoogle Scholar

  • [42] Gottlieb, M. S., R. Schroff, H. M. Schanker, J. D. Weisman, P. T. Fan, R. A. Wolf, and A. Saxon, Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency, N. Engl. J. Med., 1981, 305, 1425-1431 Google Scholar

  • [43] Doitsh, G., N. L. Galloway, X. Geng, Z. Yang, K. M. Monroe, O. Zepeda, P. W. Hunt, H. Hatano, S. Sowinski, I. Munoz-Arias, et al., Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection, Nature, 2014, 505, 509-514 Web of ScienceGoogle Scholar

  • [44] Monroe, K. M., Z. Yang, J. R. Johnson, X. Geng, G. Doitsh, N. J. Krogan, and W. C. Greene, IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV, Science, 2014, 343, 428-432 Web of ScienceGoogle Scholar

  • [45] Okoye, A. A., and L. J. Picker, CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure, Immunol. Rev., 2013, 254, 54-64 Web of ScienceGoogle Scholar

  • [46] Masters, S. L., M. Gerlic, D. Metcalf, S. Preston, M. Pellegrini, J. A. O’Donnell, K. McArthur, T. M. Baldwin, S. Chevrier, C. J. Nowell, et al., NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells, Immunity, 2012, 37, 1009-1023 Web of ScienceGoogle Scholar

  • [47] Croker, B. A., J. A. O’Donnell, and M. Gerlic, Pyroptotic death storms and cytopenia, Curr. Opin. Immunol., 2014, 26, 128-137 Web of ScienceCrossrefGoogle Scholar

  • [48] von Moltke, J., N. J. Trinidad, M. Moayeri, A. F. Kintzer, S. B. Wang, N. van Rooijen, C. R. Brown, B. A. Krantz, S. H. Leppla, K. Gronert, et al., Rapid induction of inflammatory lipid mediators by the inflammasome in vivo, Nature, 2012, 490, 107-111 Web of ScienceGoogle Scholar

  • [49] Schroder, K., K. M. Irvine, M. S. Taylor, N. J. Bokil, K. A. Le Cao, K. A. Masterman, L. I. Labzin, C. A. Semple, R. Kapetanovic, L. Fairbairn, et al., Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages, Proc. Natl. Acad. Sci. U S A, 2012, 109, E944-953 Web of ScienceGoogle Scholar

About the article

Received: 2014-10-20

Accepted: 2014-12-04

Published Online: 2015-01-14

Published in Print: 2016-01-01

Citation Information: Inflammasome, Volume 2, Issue 1, Pages 1–6, ISSN (Online) 2300-102X, DOI: https://doi.org/10.1515/infl-2015-0001.

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© 2015 Dave Boucher et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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