Jump to ContentJump to Main Navigation
Show Summary Details
More options …


Editor-in-Chief: Pelegrin, Pablo

Ed. by Lopez-Castejón, Gloria

1 Issue per year

Emerging Science

Open Access
See all formats and pricing
More options …

New insights in caspase-11 functions in noncanonical inflammasome signalling

Mélanie Bodnar
  • INSERM U1052, Centre de Recherche en Cancerologie de Lyon, F-69000 Lyon, France
  • Universite de Lyon, F-69000 Lyon, France
  • Universite Lyon 1, ISPB, Lyon, F-69622, France, F-69000 Lyon, France
  • CNRS UMR5286, Centre de Recherche en Cancerologie de Lyon, F-69000 Lyon, France
  • Centre Leon Berard, F-69008 Lyon, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Virginie Petrilli
  • Corresponding author
  • INSERM U1052, Centre de Recherche en Cancerologie de Lyon, F-69000 Lyon, France
  • Universite de Lyon, F-69000 Lyon, France
  • Universite Lyon 1, ISPB, Lyon, F-69622, France, F-69000 Lyon, France
  • CNRS UMR5286, Centre de Recherche en Cancerologie de Lyon, F-69000 Lyon, France
  • Centre Leon Berard, F-69008 Lyon, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-04-23 | DOI: https://doi.org/10.2478/infl-2014-0001


Inflammasomes are multi-protein complexes that play a crucial role in innate immunity. They are assembled by cytosolic sensors of the Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLR) and PYrin and HIN (PYHIN) domain-containing protein families upon sensing various pathogens and danger signals. Inflammasome formation culminates in caspase-1 activation, which causes the cleavage of pro-IL-1β and pro- IL-18 into active cytokines; this eventually results in the induction of an inflammatory cell death called pyroptosis. Recent data using Gram-negative bacteria suggests a role for caspase-11 not only in NLRP3 inflammasome activation but also in a caspase-1- and inflammasome-independent cell death. This novel caspase-11-dependent pathway is critical to control infection by Gram-negative bacteria and has been named the noncanonical inflammasome.

Keywords : caspase-1; cell death; cytosolic LPS; IL-1b; inflammasome


  • [1] McIlwain DR., Berger T., Mak TW., Caspase functions in cell death and disease., Cold Spring Harb. Perspect. Biol., 2013, 5, a008656Google Scholar

  • [2] Lamkanfi M., Declercq W., Kalai M., Saelens X., Vandenabeele P., Alice in caspase land. A phylogenetic analysis of caspases from worm to man., Cell Death Differ., 2002, 9, 358-61CrossrefGoogle Scholar

  • [3] Martinon F., Tschopp J., Inflammatory caspases and inflammasomes: master switches of inflammation, Cell Death Differ. 2006/09/16 ed., 2006, 14, 10-22Google Scholar

  • [4] Saleh M., Vaillancourt JP., Graham RK., Huyck M., Srinivasula SM., Alnemri ES., et al., Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms, Nature. 2004/05/07 ed., 2004, 429, 75-9Google Scholar

  • [5] Martinon F., Tschopp J., Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases, Cell., 2004, 117, 561-74Google Scholar

  • [6] Martinon F., Burns K., Tschopp J., The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta, Mol Cell., 2002, 10, 417-26CrossrefPubMedGoogle Scholar

  • [7] Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner BA., et al., Caspase-12 mediates endoplasmic-reticulumspecific apoptosis and cytotoxicity by amyloid-beta, Nature. 2000/01/19 ed., 2000, 403, 98-103Google Scholar

  • [8] Saleh M., Mathison JC., Wolinski MK., Bensinger SJ., Fitzgerald P., Droin N., et al., Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice, Nature. 2006/04/21 ed., 2006, 440, 1064-8Google Scholar

  • [9] Wang S., Miura M., Jung YK., Zhu H., Li E., Yuan J., Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE, Cell. 1998/03/10 ed., 1998, 92, 501-9Google Scholar

  • [10] Agostini L., Martinon F., Burns K., McDermott MF., Hawkins PN., Tschopp J., NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder, Immunity., 2004, 20, 319-25Google Scholar

  • [11] Mariathasan S., Newton K., Monack DM., Vucic D., French DM., Lee WP., et al., Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf, Nature., 2004, 430, 213-8Google Scholar

  • [12] Elinav E., Strowig T., Kau AL., Henao-Mejia J., Thaiss C a., Booth CJ., et al., NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis., Cell., 2011, 145, 745-57Google Scholar

  • [13] Vladimer GI., Weng D., Paquette SWM., Vanaja SK., Rathinam VAK., Aune MH., et al., The NLRP12 inflammasome recognizes Yersinia pestis., Immunity., 2012, 37, 96-107Google Scholar

  • [14] Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G., Caffrey DR., et al., AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC, Nature. 2009/01/23 ed., 2009, 458, 514-8Google Scholar

  • [15] Fernandes-Alnemri T., Yu JW., Datta P., Wu J., Alnemri ES., AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA, Nature. 2009/01/23 ed., 2009, 458, 509-13Google Scholar

  • [16] Martinon F., Gaide O., Petrilli V., Mayor A., Tschopp J., NALP inflammasomes: a central role in innate immunity, Semin Immunopathol., 2007, 29, 213-29Google Scholar

  • [17] Hu Z., Yan C., Liu P., Huang Z., Ma R., Zhang C., et al., Crystal structure of NLRC4 reveals its autoinhibition mechanism., Science., 2013, 341, 172-5Google Scholar

  • [18] Poyet JL., Srinivasula SM., Tnani M., Razmara M., Fernandes- Alnemri T., Alnemri ES., Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1., J. Biol. Chem., 2001, 276, 28309-13Google Scholar

  • [19] Miao EA., Alpuche-Aranda CM., Dors M., Clark AE., Bader MW., Miller SI., et al., Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf, Nat Immunol., 2006, 7, 569-75CrossrefGoogle Scholar

  • [20] Broz P., von Moltke J., Jones JW., Vance RE., Monack DM., Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing., Cell Host Microbe., 2010, 8, 471-83PubMedCrossrefGoogle Scholar

  • [21] Allen IC., Scull M a., Moore CB., Holl EK., McElvania-TeKippe E., Taxman DJ., et al., The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA., Immunity., 2009, 30, 556-65CrossrefGoogle Scholar

  • [22] Hise A., Tomalka J., Ganesan S., Patel K., An Essential Role for the NLRP3 Inflammasome in Host Defense against the Human Fungal Pathogen Candida albicans, Cell Host Microbe, 2009, 5, 487-97CrossrefGoogle Scholar

  • [23] Mariathasan S., Weiss DS., Newton K., McBride J., O’Rourke K., Roose-Girma M., et al., Cryopyrin activates the inflammasome in response to toxins and ATP., Nature., 2006, 440, 228-32Google Scholar

  • [24] Martinon F., Petrilli V., Mayor A., Tardivel A., Tschopp J., Gout-associated uric acid crystals activate the NALP3 inflammasome., Nature., 2006, 440, 237-41Google Scholar

  • [25] Dostert C., Petrilli V., Van Bruggen R., Steele C., Mossman BT., Tschopp J., Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica., Science., 2008, 320, 674-7Google Scholar

  • [26] Duewell P., Kono H., Rayner KJ., Sirois CM., Vladimer G., Bauernfeind FG., et al., NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals., Nature., 2010, 464, 1357-61Google Scholar

  • [27] Faustin B., Lartigue L., Bruey J-MM., Luciano F., Sergienko E., Bailly-Maitre B., et al., Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation, Mol Cell., 2007, 25, 713-24Google Scholar

  • [28] Boyden ED., Dietrich WF., Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin, Nat Genet., 2006, 38, 240-4CrossrefGoogle Scholar

  • [29] Zhao Y., Yang J., Shi J., Gong Y-N., Lu Q., Xu H., et al., The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus., Nature., 2011, 477, 596-600Google Scholar

  • [30] Strowig T., Henao-Mejia J., Elinav E., Flavell R., Inflammasomes in health and disease., Nature., 2012, 481, 278-86Google Scholar

  • [31] Fink SL., Cookson BT., Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells., Infect. Immun., 2005, 73, 1907-16Google Scholar

  • [32] Kayagaki N., Warming S., Lamkanfi M., Vande Walle L., Louie S., Dong J., et al., Non-canonical inflammasome activation targets caspase-11., Nature., 2011, 479, 117-21Google Scholar

  • [33] Kang SJ., Wang S., Hara H., Peterson EP., Namura S., Amin-Hanjani S., et al., Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions., J. Cell Biol., 2000, 149, 613-22Google Scholar

  • [34] Kuida K., Lippke JA., Ku G., Harding MW., Livingston DJ., Su MS., et al., Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme, Science (80-. )., 1995, 267, 2000-3Google Scholar

  • [35] Li P., Allen H., Banerjee S., Franklin S., Herzog L., Johnston C., et al., Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock, Cell., 1995, 80, 401-11Google Scholar

  • [36] Rathinam VAK., Vanaja SK., Waggoner L., Sokolovska A., Becker C., Stuart LM., et al., TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria., Cell., 2012, 150, 606-19Google Scholar

  • [37] Gurung P., Malireddi RKS., Anand PK., Demon D., Walle L Vande., Liu Z., et al., Toll or interleukin-1 receptor (TIR) domain- containing adaptor inducing interferon-β (TRIF)-mediated caspase-11 protease production integrates Toll-like receptor 4 (TLR4) protein- and Nlrp3 inflammasome-mediated host defense against enteropathogens., J. Biol. Chem., 2012, 287, 34474-83Google Scholar

  • [38] Aachoui Y., Leaf I a., Hagar J a., Fontana MF., Campos CG., Zak DE., et al., Caspase-11 protects against bacteria that escape the vacuole., Science., 2013, 339, 975-8Google Scholar

  • [39] Case CL., Kohler LJ., Lima JB., Strowig T., de Zoete MR., Flavell R a., et al., Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila., Proc. Natl.Acad. Sci. U. S. A., 2013, 110, 1851-6Google Scholar

  • [40] Casson CN., Copenhaver AM., Zwack EE., Nguyen HT., Strowig T., Javdan B., et al., Caspase-11 Activation in Response to Bacterial Secretion Systems that Access the Host Cytosol., PLoS Pathog., 2013, 9, e1003400CrossrefGoogle Scholar

  • [41] Broz P., Ruby T., Belhocine K., Bouley DM., Kayagaki N., Dixit VM., et al., Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1., Nature., 2012, 490, 288-91Google Scholar

  • [42] Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., et al., Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product., J. Immunol., 1999, 162, 3749-52Google Scholar

  • [43] Kayagaki N., Wong M., Stowe I., Noncanonical inflammasome activation by intracellular LPS independent of TLR4, Science (80-. )., 2013, 341, Pages: 1246-9Google Scholar

  • [44] Hagar JA., Powell DA., Aachoui Y., Ernst RK., Miao EA., Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock., Science., 2013, 341, 1250-3Google Scholar

  • [45] Schauvliege R., Vanrobaeys J., Schotte P., Beyaert R., Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1., J.Biol. Chem., 2002, 277, 41624-30Google Scholar

  • [46] Sander LE., Davis MJ., Boekschoten M V., Amsen D., Dascher CC., Ryffel B., et al., Detection of prokaryotic mRNA signifies microbial viabil Google Scholar

About the article

Received: 2013-10-21

Accepted: 2014-01-17

Published Online: 2014-04-23

Published in Print: 2014-01-01

Citation Information: Inflammasome, ISSN (Online) 2300-102X, DOI: https://doi.org/10.2478/infl-2014-0001.

Export Citation

© 2014 Mélanie Bodnar, Virginie Petrilli. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Comments (0)

Please log in or register to comment.
Log in