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NALP Inflammasomes: a central role in innate immunity

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Abstract

Inflammasomes are cytoplasmic multiprotein complexes that mediate the maturation of the proinflammatory cytokines interleukin-1β (IL-1β), IL-18, and possibly IL-33 by controlling the activation of the inflammatory caspases-1 and -5. Assembly of inflammasomes depends on NOD-like receptor (NLR) family members such as NALPs, NAIP, and IPAF. Various microbial and endogenous stimuli activate different types of inflammasomes. This article focuses on the Pyrin domain containing NLRs, known as NALP proteins. Recent findings provide exciting insights into how these proteins might be activated and also provide evidence of the critical role of the NALP inflammasomes in innate immunity and inflammatory diseases.

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Abbreviations

ASC:

Apoptosis-associated speck-like protein containing a CARD

CARD:

Caspase recruitment domain

DNFB:

2,4-dinitrofluorobenzene

ICE:

interleukin-1β -converting enzyme

IL-1:

interleukin-1

IPAF:

ICE protease-activating factor

LRR:

leucine rich repeat

MDP:

Muramyl dipeptide

MSU:

Monosodium urate crystals

MyD88:

Myeloid differentiation protein 88

NALP:

NACHT, LRR and PYD containing proteins

NACHT:

Domain present NAIP, the major histocompatibility complex (MHC) class II transactivator (CIITA), HET-E and TP1

NAIP:

Neuronal apoptosis inhibitory protein

NB-ARC:

nucleotide-binding adaptor shared by APAF-1, R gene products and CED-4

NBS-LRR:

nucleotide binding site-leucine-rich repeat

NLR:

NOD-like receptors

PAMP:

Pathogen-associated molecular patterns

PYD:

Pyrin domain

TNP-CL:

Trinitrophenylchloride

TNCB:

Trinitrochlorobenzene

References

  1. Aganna E, Martinon F, Hawkins PN, Ross JB, Swan DC, Booth DR, Lachmann HJ, Bybee A, Gaudet R, Woo P, Feighery C, Cotter FE, Thome M, Hitman GA, Tschopp J, McDermott MF (2002) Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum 46:2445–2452

    PubMed  CAS  Google Scholar 

  2. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J (2004) NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20:319–325

    PubMed  CAS  Google Scholar 

  3. Amer A, Franchi L, Kanneganti TD, Body-Malapel M, Ozoren N, Brady G, Meshinchi S, Jagirdar R, Gewirtz A, Akira S, Nunez G (2006) Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J Biol Chem 281:35217–35223

    PubMed  CAS  Google Scholar 

  4. Antonopoulos C, Cumberbatch M, Dearman RJ, Daniel RJ, Kimber I, Groves RW (2001) Functional caspase-1 is required for Langerhans cell migration and optimal contact sensitization in mice. J Immunol 166:3672–3677

    PubMed  CAS  Google Scholar 

  5. Aravind L, Dixit VM, Koonin EV (1999) The domains of death: evolution of the apoptosis machinery. Trends Biochem Sci 24:47–53

    PubMed  CAS  Google Scholar 

  6. Aravind L, Dixit VM, Koonin EV (2001) Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291:1279–1284

    PubMed  CAS  Google Scholar 

  7. Azevedo C, Betsuyaku S, Peart J, Takahashi A, Noel L, Sadanandom A, Casais C, Parker J, Shirasu K (2006) Role of SGT1 in resistance protein accumulation in plant immunity. EMBO J 25:2007–2016

    PubMed  CAS  Google Scholar 

  8. Bannert N, Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci USA 101(Suppl 2):14572–14579

    PubMed  CAS  Google Scholar 

  9. Bannert N, Kurth R (2006) The evolutionary dynamics of human endogenous retroviral families. Annu Rev Genomics Hum Genet 7:149–173

    PubMed  CAS  Google Scholar 

  10. Baumann JG (2006) Intracellular restriction factors in mammalian cells-An ancient defense system finds a modern foe. Curr HIV Res 4:141–168

    PubMed  CAS  Google Scholar 

  11. Bertin J, DiStefano PS (2000) The PYRIN domain: a novel motif found in apoptosis and inflammation proteins. Cell Death Differ 7:1273–1274

    PubMed  CAS  Google Scholar 

  12. Bhattarai KK, Li Q, Liu Y, Dinesh-Kumar SP, Kaloshian I (2007) The Mi-1-mediated pest resistance requires Hsp90 and Sgt1. Plant Physiol 144:312–323

    PubMed  CAS  Google Scholar 

  13. Boatright KM, Renatus M, Scott FL, Sperandio S, Shin H, Pedersen IM, Ricci JE, Edris WA, Sutherlin DP, Green DR, Salvesen GS (2003) A unified model for apical caspase activation. Mol Cell 11:529–541

    PubMed  CAS  Google Scholar 

  14. Bos JI, Kanneganti TD, Young C, Cakir C, Huitema E, Win J, Armstrong MR, Birch PR, Kamoun S (2006) The C-terminal half of Phytophthora infestans RXLR effector AVR3a is sufficient to trigger R3a-mediated hypersensitivity and suppress INF1-induced cell death in Nicotiana benthamiana. Plant J 48:165–176

    PubMed  CAS  Google Scholar 

  15. Boyden ED, Dietrich WF (2006) Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38:240–244

    PubMed  CAS  Google Scholar 

  16. Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC (2007) Bcl-2 and Bcl-XL Regulate Proinflammatory Caspase-1 Activation by Interaction with NALP1. Cell 129:45–56

    PubMed  CAS  Google Scholar 

  17. Buell G, Chessell IP, Michel AD, Collo G, Salazzo M, Herren S, Gretener D, Grahames C, Kaur R, Kosco-Vilbois MH, Humphrey PP (1998) Blockade of human P2X7 receptor function with a monoclonal antibody. Blood 92:3521–3528

    PubMed  CAS  Google Scholar 

  18. Burger D, Dayer JM, Palmer G, Gabay C (2006) Is IL-1 a good therapeutic target in the treatment of arthritis? Best Pract Res Clin Rheumatol 20:879–896

    PubMed  CAS  Google Scholar 

  19. Caillaud M, Duchamp G, Gerard N (2005) In vivo effect of interleukin-1beta and interleukin-1RA on oocyte cytoplasmic maturation, ovulation, and early embryonic development in the mare. Reprod Biol Endocrinol 3:26

    PubMed  Google Scholar 

  20. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA et al (1992) Molecular cloning of the interleukin-1 beta converting enzyme. Science 256:97–100

    PubMed  CAS  Google Scholar 

  21. Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock KL (2006) MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 116:2262–2271

    PubMed  CAS  Google Scholar 

  22. Church LD, Churchman SM, Hawkins PN, McDermott MF (2006) Hereditary auto-inflammatory disorders and biologics. Springer Semin Immunopathol 27:494–508

    PubMed  CAS  Google Scholar 

  23. Cornelis S, Kersse K, Festjens N, Lamkanfi M, Vandenabeele P (2007) Inflammatory caspases: targets for novel therapies. Curr Pharm Des 13:365–383

    Google Scholar 

  24. da Silva Correira J, Miranda Y, Leonard N, Ulevitch RJ (2007) SGT1 is essential for NOD1 activation. Proc Natl Acad Sci USA 104:6764–6769

    Google Scholar 

  25. Dade S, Callebaut I, Paillisson A, Bontoux M, Dalbies-Tran R, Monget P (2004) In silico identification and structural features of six new genes similar to MATER specifically expressed in the oocyte. Biochem Biophys Res Commun 324:547–553

    PubMed  CAS  Google Scholar 

  26. Dalbies-Tran R, Papillier P, Pennetier S, Uzbekova S, Monget P (2005) Bovine mater-like NALP9 is an oocyte marker gene. Mol Reprod Dev 71:414–421

    PubMed  CAS  Google Scholar 

  27. Deschamps S, Meyer J, Chatterjee G, Wang H, Lengyel P, Roe BA (2003) The mouse Ifi200 gene cluster: genomic sequence, analysis, and comparison with the human HIN-200 gene cluster. Genomics 82:34–46

    PubMed  CAS  Google Scholar 

  28. Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC (1999) Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 18:5242–5251

    PubMed  CAS  Google Scholar 

  29. DeYoung BJ, Innes RW (2006) Plant NBS-LRR proteins in pathogen sensing and host defense. Nat Immunol 7:1243–1249

    PubMed  CAS  Google Scholar 

  30. Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, Figari IS, Palladino MA Jr, O’Connor JV (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 163:1433–1450

    PubMed  CAS  Google Scholar 

  31. Dinarello CA, Fantuzzi G (2003) Interleukin-18 and host defense against infection. J Infect Dis 187(Suppl 2):S370–S384

    PubMed  CAS  Google Scholar 

  32. Dinarello CA (2004) Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 10:201–222

    PubMed  CAS  Google Scholar 

  33. Dode C, Le Du N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G, Meyrier A, Watts RA, Scott DG, Nicholls A, Granel B, Frances C, Garcier F, Edery P, Boulinguez S, Domergues JP, Delpech M, Grateau G (2002) New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. Am J Hum Genet 70:1498–1506

    PubMed  CAS  Google Scholar 

  34. Endrizzi MG, Hadinoto V, Growney JD, Miller W, Dietrich WF (2000) Genomic sequence analysis of the mouse Naip gene array. Genome Res 10:1095–1102

    PubMed  CAS  Google Scholar 

  35. Fairbrother WJ, Gordon NC, Humke EW, O’Rourke KM, Starovasnik MA, Yin JP, Dixit VM (2001) The PYRIN domain: a member of the death domain-fold superfamily. Protein Sci 10:1911–1918

    PubMed  CAS  Google Scholar 

  36. Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, Volkmann N, Hanein D, Rouiller I, Reed JC (2007) Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25:713–724

    PubMed  CAS  Google Scholar 

  37. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F (2006) The P2X7 receptor: a key player in IL-1 processing and release. J Immunol 176:3877–3883

    PubMed  CAS  Google Scholar 

  38. Fesik SW (2000) Insights into programmed cell death through structural biology [In process citation]. Cell 103:273–282

    PubMed  CAS  Google Scholar 

  39. FrenchFMFConsortium (1997) A candidate gene for familial Mediterranean fever. The French FMF Consortium. Nat Genet 17:25–31

    Google Scholar 

  40. Fritz JH, Ferrero RL, Philpott DJ, Girardin SE (2006) Nod-like proteins in immunity, inflammation and disease. Nat Immunol 7:1250–1257

    PubMed  CAS  Google Scholar 

  41. Fujisawa A, Kambe N, Saito M, Nishikomori R, Tanizaki H, Kanazawa N, Adachi S, Heike T, Sagara J, Suda T, Nakahata T, Miyachi Y (2006) Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. Blood

  42. Gauthier Y, Cario-Andre M, Lepreux S, Pain C, Taieb A (2003) Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo. Br J Dermatol 148:95–101

    PubMed  CAS  Google Scholar 

  43. Gavrilin MA, Bouakl IJ, Knatz NL, Duncan MD, Hall MW, Gunn JS, Wewers MD (2006) Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc Natl Acad Sci USA 103:141–146

    PubMed  CAS  Google Scholar 

  44. Gerard N, Caillaud M, Martoriati A, Goudet G, Lalmanach AC (2004) The interleukin-1 system and female reproduction. J Endocrinol 180:203–212

    PubMed  CAS  Google Scholar 

  45. Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A, Quintal L, Sekut L, Talanian R, Paskind M, Wong W, Kamen R, Tracey D, Allen H (1997) Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386:619–623

    PubMed  CAS  Google Scholar 

  46. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O’Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 355:581–592

    PubMed  CAS  Google Scholar 

  47. Grabbe S, Schwarz T (1998) Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today 19:37–44

    PubMed  CAS  Google Scholar 

  48. Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming MA, Hayashi N, Higashino K, Okamura H, Nakanishi K, Kurimoto M, Tanimoto T, Flavell RA, Sato V, Harding MW, Livingston DJ, Su MS (1997) Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science 275:206–209

    PubMed  CAS  Google Scholar 

  49. Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MS (2004) Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet 13:2263–2278

    PubMed  CAS  Google Scholar 

  50. Hawkins PN, Lachmann HJ, McDermott MF (2003) Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med 348:2583–2584

    PubMed  Google Scholar 

  51. Herskovits AA, Auerbuch V, Portnoy DA (2007) Bacterial ligands generated in a phagosome are targets of the cytosolic innate immune system. PLoS Pathog 3:e51

    PubMed  Google Scholar 

  52. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305

    PubMed  CAS  Google Scholar 

  53. Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL, Anderson JP, Wanderer AA, Firestein GS (2004) Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 364:1779–1785

    PubMed  CAS  Google Scholar 

  54. Hofmann K (1999) The modular nature of apoptotic signaling proteins. Cell Mol Life Sci 55:1113–1128

    PubMed  CAS  Google Scholar 

  55. Hogquist KA, Nett MA, Unanue ER, Chaplin DD (1991) Interleukin 1 is processed and released during apoptosis. Proc Natl Acad Sci USA 88:8485–8489

    PubMed  CAS  Google Scholar 

  56. Holt BF 3rd, Belkhadir Y, Dangl JL (2005) Antagonistic control of disease resistance protein stability in the plant immune system. Science 309:929–932

    PubMed  CAS  Google Scholar 

  57. Horikawa M, Kirkman NJ, Mayo KE, Mulders SM, Zhou J, Bondy CA, Hsu SY, King GJ, Adashi EY (2005) The mouse germ-cell-specific leucine-rich repeat protein NALP14: a member of the NACHT nucleoside triphosphatase family. Biol Reprod 72:879–889

    PubMed  CAS  Google Scholar 

  58. Hubert DA, Tornero P, Belkhadir Y, Krishna P, Takahashi A, Shirasu K, Dangl JL (2003) Cytosolic HSP90 associates with and modulates the Arabidopsis RPM1 disease resistance protein. EMBO J 22:5679–5689

    PubMed  CAS  Google Scholar 

  59. Inohara, Chamaillard, McDonald C, Nunez G (2005) NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 74:355–383

    PubMed  CAS  Google Scholar 

  60. Inokuchi T, Moriwaki Y, Tsutsui H, Yamamoto A, Takahashi S, Tsutsumi Z, Ka T, Nakanishi K, Yamamoto T (2006) Plasma interleukin (IL)-18 (interferon-gamma-inducing factor) and other inflammatory cytokines in patients with gouty arthritis and monosodium urate monohydrate crystal-induced secretion of IL-18. Cytokine 33:21–27

    PubMed  CAS  Google Scholar 

  61. InternationalFMFConsortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 90:797–807

    Google Scholar 

  62. Jarvelainen HA, Galmiche A, Zychlinsky A (2003) Caspase-1 activation by Salmonella. Trends Cell Biol 13:204–209

    PubMed  Google Scholar 

  63. Jiang X, Wang X (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem 73:87–106

    PubMed  CAS  Google Scholar 

  64. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G, Bennett DC, Fain PR, Spritz RA (2007) NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 356:1216–1225

    PubMed  CAS  Google Scholar 

  65. Johnston JB, Barrett JW, Nazarian SH, Goodwin M, Ricuttio D, Wang G, McFadden G (2005) A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 23:587–598

    PubMed  CAS  Google Scholar 

  66. Johnstone RW, Trapani JA (1999) Transcription and growth regulatory functions of the HIN-200 family of proteins. Mol Cell Biol 19:5833–5838

    PubMed  CAS  Google Scholar 

  67. Jones JD, Dangl JL (2006) The plant immune system. Nature 444:323–329

    PubMed  CAS  Google Scholar 

  68. Kahlenberg JM, Dubyak GR (2004) Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ release. Am J Physiol Cell Physiol 286:C1100–1108

    PubMed  CAS  Google Scholar 

  69. Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P, Bertin J, Coyle A, Grant EP, Akira S, Nunez G (2006) Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440:233–236

    PubMed  CAS  Google Scholar 

  70. Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725–732

    PubMed  CAS  Google Scholar 

  71. Kostura MJ, Tocci MJ, Limjuco G, Chin J, Cameron P, Hillman AG, Chartrain NA, Schmidt JA (1989) Identification of a monocyte specific pre-interleukin 1 beta convertase activity. Proc Natl Acad Sci USA 86:5227–5231

    PubMed  CAS  Google Scholar 

  72. Kramer M, Netea MG, de Jong DJ, Kullberg BJ, Adema GJ (2006) Impaired dendritic cell function in Crohn’s disease patients with NOD2 3020insC mutation. J Leukoc Biol 79:860–866

    PubMed  CAS  Google Scholar 

  73. Krueger JM, Majde JA (2003) Humoral links between sleep and the immune system: research issues. Ann NY Acad Sci 992:9–20

    Article  PubMed  CAS  Google Scholar 

  74. Kufer TA, Banks DJ, Philpott DJ (2006) Innate immune sensing of microbes by Nod proteins. Ann NY Acad Sci 1072:19–27

    PubMed  CAS  Google Scholar 

  75. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS, Flavell RA (1995) Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 267:2000–2003

    PubMed  CAS  Google Scholar 

  76. Labasi JM, Petrushova N, Donovan C, McCurdy S, Lira P, Payette MM, Brissette W, Wicks JR, Audoly L, Gabel CA (2002) Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response. J Immunol 168:6436–6445

    PubMed  CAS  Google Scholar 

  77. Landolfo S, Gariglio M, Gribaudo G, Lembo D (1998) The Ifi 200 genes: an emerging family of IFN-inducible genes. Biochimie 80:721–728

    PubMed  CAS  Google Scholar 

  78. Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J, Coyle AJ, Flavell RA, Galan JE (2006) Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med 203:1407–1412

    PubMed  CAS  Google Scholar 

  79. Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK (1996) Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 148:1219–1228

    PubMed  Google Scholar 

  80. Leister RT, Dahlbeck D, Day B, Li Y, Chesnokova O, Staskawicz BJ (2005) Molecular genetic evidence for the role of SGT1 in the intramolecular complementation of Bs2 protein activity in Nicotiana benthamiana. Plant Cell 17:1268–1278

    PubMed  CAS  Google Scholar 

  81. Li H, Nookala S, Re F (2007) Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol 178:5271–5276

    PubMed  CAS  Google Scholar 

  82. Li P, Allen H, Banerjee S, Franklin S, Herzog L, Johnston C, McDowell J, Paskind M, Rodman L, Salfeld J et al (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80:401–411

    PubMed  CAS  Google Scholar 

  83. Lich JD, Williams KL, Moore CB, Arthur JC, Davis BK, Taxman DJ, Ting JP (2007) Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes. J Immunol 178:1256–1260

    PubMed  CAS  Google Scholar 

  84. Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M, Gromnica-Ihle E, Antoni C, Herzer P, Kekow J, Schneider M, Zink A (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412

    PubMed  CAS  Google Scholar 

  85. Liu Y, Burch-Smith T, Schiff M, Feng S, Dinesh-Kumar SP (2004) Molecular chaperone Hsp90 associates with resistance protein N and its signaling proteins SGT1 and Rar1 to modulate an innate immune response in plants. J Biol Chem 279:2101–2108

    PubMed  CAS  Google Scholar 

  86. Lucas SM, Rothwell NJ, Gibson RM (2006) The role of inflammation in CNS injury and disease. Br J Pharmacol 147(Suppl 1):S232–S240

    PubMed  CAS  Google Scholar 

  87. Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M (2005) Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307:734–738

    PubMed  CAS  Google Scholar 

  88. Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110:851–860

    PubMed  CAS  Google Scholar 

  89. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM (2004) Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213–218

    PubMed  CAS  Google Scholar 

  90. Mariathasan S, Weiss DS, Dixit VM, Monack DM (2005) Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. J Exp Med 202:1043–1049

    PubMed  CAS  Google Scholar 

  91. Mariathasan S, Weiss DS, Newton K, McBride J, O’Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232

    PubMed  CAS  Google Scholar 

  92. Mariathasan S, Monack DM (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7:31–40

    PubMed  CAS  Google Scholar 

  93. Martinon F, Hofmann K, Tschopp J (2001) The Pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation. Curr Biol 10:R118–R120

    Google Scholar 

  94. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426

    PubMed  CAS  Google Scholar 

  95. Martinon F, Agostini L, Meylan E, Tschopp J (2004) Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol 14:1929–1934

    PubMed  CAS  Google Scholar 

  96. Martinon F, Tschopp J (2004) Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117:561–574

    PubMed  CAS  Google Scholar 

  97. Martinon F, Tschopp J (2005) NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26:447–454

    PubMed  CAS  Google Scholar 

  98. Martinon F, Glimcher LH (2006) Gout: new insights into an old disease. J Clin Invest 116:2073–2075

    PubMed  CAS  Google Scholar 

  99. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241

    PubMed  CAS  Google Scholar 

  100. Martinon F, Tschopp J (2007) Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ 14:10–22

    PubMed  CAS  Google Scholar 

  101. Masters SL, Lobito AA, Chae J, Kastner DL (2006) Recent advances in the molecular pathogenesis of hereditary recurrent fevers. Curr Opin Allergy Clin Immunol 6:428–433

    Article  PubMed  CAS  Google Scholar 

  102. Matos TJ, Jaleco SP, Goncalo M, Duarte CB, Lopes MC (2005) Release of IL-1beta via IL-1beta-converting enzyme in a skin dendritic cell line exposed to 2,4-dinitrofluorobenzene. Mediat Inflamm 2005:131–138

    Google Scholar 

  103. Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    PubMed  CAS  Google Scholar 

  104. Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J (2007) A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses Nat Immunol 8:497–503

    Google Scholar 

  105. McCulloch CA, Downey GP, El-Gabalawy H (2006) Signalling platforms that modulate the inflammatory response: new targets for drug development. Nat Rev Drug Discov 5:864–876

    PubMed  CAS  Google Scholar 

  106. McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3:e297

    PubMed  Google Scholar 

  107. Medzhitov R, Janeway CA Jr (1998) An ancient system of host defense. Curr Opin Immunol 10:12–15

    PubMed  CAS  Google Scholar 

  108. Mestre P, Baulcombe DC (2006) Elicitor-mediated oligomerization of the tobacco N disease resistance protein. Plant Cell 18:491–501

    PubMed  CAS  Google Scholar 

  109. Miller DK, Ayala JM, Egger LA, Raju SM, Yamin TT, Ding GJ, Gaffney EP, Howard AD, Palyha OC, Rolando AM et al (1993) Purification and characterization of active human interleukin-1 beta-converting enzyme from THP.1 monocytic cells. J Biol Chem 268:18062–18069

    PubMed  CAS  Google Scholar 

  110. Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau GA, Slim R (2006) Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat Genet 38:300–302

    PubMed  CAS  Google Scholar 

  111. Muskett P, Parker J (2003) Role of SGT1 in the regulation of plant R gene signalling. Microbes Infect 5:969–976

    PubMed  CAS  Google Scholar 

  112. Nagao S, Nakanishi M, Kutsukake H, Yagawa K, Kusumoto S, Shiba T, Tanaka A, Kotani S (1990) Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs. Infect Immun 58:536–542

    PubMed  CAS  Google Scholar 

  113. Nakao S, Kuwano T, Tsutsumi-Miyahara C, Ueda S, Kimura YN, Hamano S, Sonoda KH, Saijo Y, Nukiwa T, Strieter RM, Ishibashi T, Kuwano M, Ono M (2005) Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. J Clin Invest 115:2979–2991

    PubMed  CAS  Google Scholar 

  114. Naughton GK, Eisinger M, Bystryn JC (1983) Antibodies to normal human melanocytes in vitiligo. J Exp Med 158:246–251

    PubMed  CAS  Google Scholar 

  115. Netea MG, Ferwerda G, de Jong DJ, Girardin SE, Kullberg BJ, van der Meer JW (2005) NOD2 3020insC mutation and the pathogenesis of Crohn’s disease: impaired IL-1beta production points to a loss-of-function phenotype. Neth J Med 63:305–308

    PubMed  CAS  Google Scholar 

  116. Nisole S, Stoye JP, Saib A (2005) TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 3:799–808

    PubMed  CAS  Google Scholar 

  117. Ozoren N, Masumoto J, Franchi L, Kanneganti TD, Body-Malapel M, Erturk I, Jagirdar R, Zhu L, Inohara N, Bertin J, Coyle A, Grant EP, Nunez G (2006) Distinct roles of TLR2 and the adaptor ASC in IL-1beta/IL-18 secretion in response to Listeria monocytogenes. J Immunol 176:4337–4342

    PubMed  Google Scholar 

  118. Pan Q, Mathison J, Fearns C, Kravchenko VV, Correia JD, Hoffman HM, Kobayashi KS, Bertin J, Grant EP, Coyle AJ, Sutterwala FS, Ogura Y, Flavell RA, Ulevitch RJ (2007) MDP-induced interleukin-1{beta} processing requires Nod2 and CIAS1/NALP3. J Leukoc Biol

  119. Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H (2007) The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu Rev Immunol

  120. Pawlowski K, Pio F, Chu Z, Reed JC, Godzik A (2001) PAAD- a new protein domain associated with apoptosis, cancer and autoimmune diseases. Trends Biochem Sci 26:85–87

    PubMed  CAS  Google Scholar 

  121. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082

    PubMed  CAS  Google Scholar 

  122. Pelegrin P, Surprenant A (2007) Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem 282:2386–2394

    PubMed  CAS  Google Scholar 

  123. Perregaux DG, McNiff P, Laliberte R, Conklyn M, Gabel CA (2000) ATP acts as an agonist to promote stimulus-induced secretion of IL-1 beta and IL-18 in human blood. J Immunol 165:4615–4623

    PubMed  CAS  Google Scholar 

  124. Peter ME, Krammer PH (2003) The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10:26–35

    PubMed  CAS  Google Scholar 

  125. Ponsuksili S, Brunner RM, Goldammer T, Kuhn C, Walz C, Chomdej S, Tesfaye D, Schellander K, Wimmers K, Schwerin M (2006) Bovine NALP5, NALP8, and NALP9 genes: assignment to a QTL region and the expression in adult tissues, oocytes, and preimplantation embryos. Biol Reprod 74:577–584

    PubMed  CAS  Google Scholar 

  126. Pop C, Timmer J, Sperandio S, Salvesen GS (2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22:269–275

    PubMed  CAS  Google Scholar 

  127. Poyet JL, Srinivasula SM, Tnani M, Razmara M, Fernandes-Alnemri T, Alnemri ES (2001) Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J Biol Chem 276:28309–28313

    PubMed  CAS  Google Scholar 

  128. Rock KL, Hearn A, Chen CJ, Shi Y (2005) Natural endogenous adjuvants. Springer Semin Immunopathol 26:231–246

    PubMed  Google Scholar 

  129. Romanish MT, Lock WM, de Lagemaat LN, Dunn CA, Mager DL (2007) Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution. PLoS Genet 3:e10

    PubMed  Google Scholar 

  130. Roper RJ, Ma RZ, Biggins JE, Butterfield RJ, Michael SD, Tung KS, Doerge RW, Teuscher C (2002) Interacting quantitative trait loci control loss of peripheral tolerance and susceptibility to autoimmune ovarian dysgenesis after day 3 thymectomy in mice. J Immunol 169:1640–1646

    PubMed  CAS  Google Scholar 

  131. Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X et al (1995) The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80:167–178

    PubMed  CAS  Google Scholar 

  132. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475

    PubMed  CAS  Google Scholar 

  133. Sansonetti PJ, Phalipon A, Arondel J, Thirumalai K, Banerjee S, Akira S, Takeda K, Zychlinsky A (2000) Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation. Immunity 12:581–590

    PubMed  CAS  Google Scholar 

  134. Sanz JM, Di Virgilio F (2000) Kinetics and mechanism of ATP-dependent IL-1 beta release from microglial cells. J Immunol 164:4893–4898

    PubMed  CAS  Google Scholar 

  135. Schneider DS (2002) Plant immunity and film Noir: what gumshoe detectives can teach us about plant-pathogen interactions. Cell 109:537–540

    PubMed  CAS  Google Scholar 

  136. Sehgal VN, Srivastava G (2006) Vitiligo: auto-immunity and immune responses. Int J Dermatol 45:583–590

    PubMed  Google Scholar 

  137. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521

    PubMed  CAS  Google Scholar 

  138. Shornick LP, De Togni P, Mariathasan S, Goellner J, Strauss-Schoenberger J, Karr RW, Ferguson TA, Chaplin DD (1996) Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone. J Exp Med 183:1427–1436

    PubMed  CAS  Google Scholar 

  139. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314:268–274

    PubMed  Google Scholar 

  140. Sjoholm A (1998) Aspects of the involvement of interleukin-1 and nitric oxide in the pathogenesis of insulin-dependent diabetes mellitus. Cell Death Differ 5:461–468

    PubMed  CAS  Google Scholar 

  141. Slim R, Mehio A (2007) The genetics of hydatidiform moles: new lights on an ancient disease. Clin Genet 71:25–34

    PubMed  CAS  Google Scholar 

  142. So A, De Smedt T, Revaz S, Tschopp J (2007) A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 9:R28

    PubMed  Google Scholar 

  143. Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, Griffiths RJ, Gabel CA (2001) Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem 276:125–132

    PubMed  CAS  Google Scholar 

  144. Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES (2002) The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 277:21119–21122

    PubMed  CAS  Google Scholar 

  145. Stack JH, Beaumont K, Larsen PD, Straley KS, Henkel GW, Randle JC, Hoffman HM (2005) IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients. J Immunol 175:2630–2634

    PubMed  CAS  Google Scholar 

  146. Staruch MJ, Wood DD (1982) Genetic influences on the adjuvanticity of muramyl dipeptide in vivo. J Immunol 128:155–160

    PubMed  CAS  Google Scholar 

  147. Staub E, Dahl E, Rosenthal A (2001) The DAPIN family: a novel domain links apoptotic and interferon response proteins. Trends Biochem Sci 26:83–85

    PubMed  CAS  Google Scholar 

  148. Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, Bertin J, Coyle AJ, Galan JE, Askenase PW, Flavell RA (2006) Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24:317–327

    PubMed  CAS  Google Scholar 

  149. Takehara Y, Dharmarajan AM, Kaufman G, Wallach EE (1994) Effect of interleukin-1 beta on ovulation in the in vitro perfused rabbit ovary. Endocrinology 134:1788–1793

    PubMed  CAS  Google Scholar 

  150. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774

    PubMed  CAS  Google Scholar 

  151. Tinel A, Tschopp J (2004) The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304:843–846

    PubMed  CAS  Google Scholar 

  152. Ting JP, Davis BK (2005) CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol 23:387–414

    PubMed  CAS  Google Scholar 

  153. Tong ZB, Gold L, Pfeifer KE, Dorward H, Lee E, Bondy CA, Dean J, Nelson LM (2000) Mater, a maternal effect gene required for early embryonic development in mice. Nat Genet 26:267–268

    PubMed  CAS  Google Scholar 

  154. Tong ZB, Bondy CA, Zhou J, Nelson LM (2002) A human homologue of mouse Mater, a maternal effect gene essential for early embryonic development. Hum Reprod 17:903–911

    PubMed  CAS  Google Scholar 

  155. Tschopp J, Martinon F, Burns K (2003) NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 4:95–104

    PubMed  CAS  Google Scholar 

  156. Van der Biezen EA, Jones JD (1998) Plant disease-resistance proteins and the gene-for-gene concept. Trends Biochem Sci 23:454–456

    PubMed  Google Scholar 

  157. van der Velden AW, Velasquez M, Starnbach MN (2003) Salmonella rapidly kill dendritic cells via a caspase-1-dependent mechanism. J Immunol 171:6742–6749

    PubMed  Google Scholar 

  158. van Heel DA, Ghosh S, Butler M, Hunt KA, Lundberg AM, Ahmad T, McGovern DP, Onnie C, Negoro K, Goldthorpe S, Foxwell BM, Mathew CG, Forbes A, Jewell DP, Playford RJ (2005) Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn’s disease. Lancet 365:1794–1796

    PubMed  Google Scholar 

  159. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, Dinarello CA, Apte RN (2003) IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 100:2645–2650

    PubMed  CAS  Google Scholar 

  160. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA, Kuida K, Randle J (2007) VX-765, an orally available selective interleukin converting enzyme (ICE)/caspase-1 inhibitor exhibits potent anti-inflammatory activities by inhibiting the release of IL-1b and IL-18. J Pharmacol Exp Ther

  161. Watanabe H, Gaide O, Petrilli V, Martinon F, Contassot E, Roques S, Kummer JA, Tschopp J, French LE (2007) Activation of the IL-1b-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol 127:1956–1963

    Google Scholar 

  162. Weiss DS, Henry T, Monack DM (2007) Francisella tularensis activation of the inflammasome. Ann NY Acad Sci

  163. Werts C, Girardin SE, Philpott DJ (2006) TIR, CARD and PYRIN: three domains for an antimicrobial triad. Cell Death Differ 13:798–815

    PubMed  CAS  Google Scholar 

  164. Williams KL, Taxman DJ, Linhoff MW, Reed W, Ting JP (2003) Cutting edge: Monarch-1: a pyrin/nucleotide-binding domain/leucine-rich repeat protein that controls classical and nonclassical MHC class I genes. J Immunol 170:5354–5358

    PubMed  CAS  Google Scholar 

  165. Williams KL, Lich JD, Duncan JA, Reed W, Rallabhandi P, Moore C, Kurtz S, Coffield VM, Accavitti-Loper MA, Su L, Vogel SN, Braunstein M, Ting JP (2005) The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals. J Biol Chem 280:39914–39924

    PubMed  CAS  Google Scholar 

  166. Yan N, Shi Y (2005) Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol 21:35–56

    PubMed  CAS  Google Scholar 

  167. Zamboni DS, Kobayashi KS, Kohlsdorf T, Ogura Y, Long EM, Vance RE, Kuida K, Mariathasan S, Dixit VM, Flavell RA, Dietrich WF, Roy CR (2006) The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunol 7:318–325

    PubMed  CAS  Google Scholar 

  168. Zipfel C, Felix G (2005) Plants and animals: a different taste for microbes? Curr Opin Plant Biol 8:353–360

    PubMed  CAS  Google Scholar 

  169. Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J (2007) Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ, DOI 10.1038/sj.cdd.4402195

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Acknowledgments

We thank the members of the Tschopp laboratory and Michael McDermott for discussions and critical reading of the manuscript. This work was supported by grants of the Swiss National Science Foundation (JT). FM is supported by a long-term fellowship from the Human Frontier Sciences Program. VP is supported by the EIF Marie Curie Fellowship.

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  1. Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave, Boston, MA, 02115, USA

    Fabio Martinon

  2. Department of Dermatology and Patholog-Immunology, Geneva University Medical Center, Rue Michel-Servet 1, 1211, Geneva, Switzerland

    Olivier Gaide

  3. Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland

    Virgine Pétrilli, Annick Mayor & Jürg Tschopp

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  1. Fabio Martinon
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  5. Jürg Tschopp
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Correspondence to Fabio Martinon.

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Martinon, F., Gaide, O., Pétrilli, V. et al. NALP Inflammasomes: a central role in innate immunity. Semin Immunopathol 29, 213–229 (2007). https://doi.org/10.1007/s00281-007-0079-y

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