Cellular and Molecular Life Sciences

, Volume 73, Issue 11–12, pp 2349–2367 | Cite as

The intersection of cell death and inflammasome activation

  • James E. VinceEmail author
  • John Silke
Multi-author review


Inflammasomes sense cellular danger to activate the cysteine-aspartic protease caspase-1, which processes precursor interleukin-1β (IL-1β) and IL-18 into their mature bioactive fragments. In addition, activated caspase-1 or the related inflammatory caspase, caspase-11, can cleave gasdermin D to induce a lytic cell death, termed pyroptosis. The intertwining of IL-1β activation and cell death is further highlighted by research showing that the extrinsic apoptotic caspase, caspase-8, may, like caspase-1, directly process IL-1β, activate the NLRP3 inflammasome itself, or bind to inflammasome complexes to induce apoptotic cell death. Similarly, RIPK3- and MLKL-dependent necroptotic signaling can activate the NLRP3 inflammasome to drive IL-1β inflammatory responses in vivo. Here, we review the mechanisms by which cell death signaling activates inflammasomes to initiate IL-1β-driven inflammation, and highlight the clinical relevance of these findings to heritable autoinflammatory diseases. We also discuss whether the act of cell death can be separated from IL-1β secretion and evaluate studies suggesting that several cell death regulatory proteins can directly interact with, and modulate the function of, inflammasome and IL-1β containing protein complexes.


Inflammasome Necroptosis Pyroptosis Apoptosis Caspase-1 Caspase-8 RIPK3 MLKL 



The authors’ work is supported by National Health and Medical Research (Canberra, Australia) Project grants (JEV: 1051210, 1101405), fellowships (JEV: 1052598 and JS: 541901, 1058190) and operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.The Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  2. 2.Department of Medical BiologyThe University of MelbourneParkvilleAustralia

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