Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflammasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.


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Literature Cited

  1. Dinarello CA, Simon A, van der Meer JWM. 1.  2012. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat. Rev. Drug Discov. 11:633–52 [Google Scholar]
  2. Schroder K, Tschopp J. 2.  2010. The inflammasomes. Cell 140:821–32 [Google Scholar]
  3. Garlanda C, Dinarello CA, Mantovani A. 3.  2013. The interleukin-1 family: back to the future. Immunity 39:1003–18 [Google Scholar]
  4. Hacham M, Argov S, White RM, Segal S, Apte RN. 4.  2002. Different patterns of interleukin-1alpha and interleukin-1beta expression in organs of normal young and old mice. Eur. Cytokine Netw. 13:55–65 [Google Scholar]
  5. Kurt-Jones EA, Virgin HW, Unanue ER. 5.  1985. Relationship of macrophage Ia and membrane IL 1 expression to antigen presentation. J. Immunol. 135:3652–54 [Google Scholar]
  6. Kurt-Jones EA, Beller DI, Mizel SB, Unanue ER. 6.  1985. Identification of a membrane-associated interleukin 1 in macrophages. PNAS 82:1204–8 [Google Scholar]
  7. Kaplanski G, Farnarier C, Kaplanski S, Porat R, Shapiro L. 7.  et al. 1994. Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism. Blood 84:4242–48 [Google Scholar]
  8. Miller ACK, Schattenberg DG, Malkinson AM, Ross D. 8.  1994. Decreased content of the IL1α processing enzyme calpain in murine bone marrow-derived macrophages after treatment with the benzene metabolite hydroquinone. Toxicol. Lett. 74:177–84 [Google Scholar]
  9. Groß O, Yazdi AS, Thomas CJ, Masin M, Heinz LX. 9.  et al. 2012. Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36:388–400 [Google Scholar]
  10. Yazdi AS, Drexler SK. 10.  2013. Regulation of interleukin 1α secretion by inflammasomes. Ann. Rheum. Dis. 72:Suppl. 2ii96–99 [Google Scholar]
  11. Kawaguchi Y, Nishimagi E, Tochimoto A, Kawamoto M, Katsumata Y. 11.  et al. 2006. Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts. PNAS 103:14501–6 [Google Scholar]
  12. Cohen I, Rider P, Carmi Y, Braiman A, Dotan S. 12.  et al. 2010. Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. PNAS 107:2574–79 [Google Scholar]
  13. Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA. 13.  et al. 2009. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J. Immunol. 183:4705–14 [Google Scholar]
  14. Rider P, Carmi Y, Guttman O, Braiman A, Cohen I. 14.  et al. 2011. IL-1α and IL-1β recruit different myeloid cells and promote different stages of sterile inflammation. J. Immunol. 187:4835–43 [Google Scholar]
  15. Luheshi NM, Kovács KJ, Lopez-Castejon G, Brough D, Denes A. 15.  2011. Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues. J. Neuroinflammation 8:186 [Google Scholar]
  16. Thornton P, Pinteaux E, Gibson RM, Allan SM, Rothwell NJ. 16.  2006. Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase activation and free radical release. J. Neurochem. 98:258–66 [Google Scholar]
  17. Gawaz M, Brand K, Dickfeld T, Pogatsa-Murray G, Page S. 17.  et al. 2000. Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis. Atherosclerosis 148:75–85 [Google Scholar]
  18. Kamari Y, Werman-Venkert R, Shaish A, Werman A, Harari A. 18.  et al. 2007. Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism. Atherosclerosis 195:31–38 [Google Scholar]
  19. Dinarello CA. 19.  2011. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:3720–32 [Google Scholar]
  20. Martinon F, Mayor A, Tschopp J. 20.  2009. The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27:229–65 [Google Scholar]
  21. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. 21.  2004. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20:319–25 [Google Scholar]
  22. Dinarello CA, Bendtzen K, Wolff SM. 22.  1982. Studies on the active site of human leukocytic pyrogen. Inflammation 6:63–78 [Google Scholar]
  23. Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JWM, Joosten LAB. 23.  2010. IL-1β processing in host defense: beyond the inflammasomes. PLOS Pathog. 6:e1000661 [Google Scholar]
  24. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J. 24.  et al. 2006. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N. Engl. J. Med. 355:581–92 [Google Scholar]
  25. Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. 25.  2006. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24:677–88 [Google Scholar]
  26. Dong C. 26.  2008. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 8:337–48 [Google Scholar]
  27. van de Veerdonk FL, Netea MG, Dinarello CA, Joosten LAB. 27.  2011. Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 32:110–16 [Google Scholar]
  28. Smeekens SP, van de Veerdonk FL, van der Meer JWM, Kullberg BJ, Joosten LAB, Netea MG. 28.  2010. The Candida Th17 response is dependent on mannan- and β-glucan-induced prostaglandin E2. Int. Immunol. 22:889–95 [Google Scholar]
  29. Moreira-Teixeira L, Resende M, Coffre M, Devergne O, Herbeuval JP. 29.  et al. 2011. Proinflammatory environment dictates the IL-17–producing capacity of human invariant NKT cells. J. Immunol. 186:5758–65 [Google Scholar]
  30. Hughes T, Becknell B, Freud AG, McClory S, Briercheck E. 30.  et al. 2010. Interleukin-1β selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. Immunity 32:803–14 [Google Scholar]
  31. Dinarello CA. 31.  1996. Biologic basis for interleukin-1 in disease. Blood 87:2095–147 [Google Scholar]
  32. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E. 32.  et al. 2005. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–90 [Google Scholar]
  33. Cayrol C, Girard JP. 33.  2009. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. PNAS 106:9021–26 [Google Scholar]
  34. Louten J, Rankin AL, Li Y, Murphy EE, Beaumont M. 34.  et al. 2011. Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation. Int. Immunol. 23:307–15 [Google Scholar]
  35. Matsuba-Kitamura S, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Taki Y. 35.  et al. 2010. Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis. Int. Immunol. 22:479–89 [Google Scholar]
  36. Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y. 36.  et al. 2012. Contribution of IL-33–activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. PNAS 109:3451–56 [Google Scholar]
  37. Stevenson FT, Turck J, Locksley RM, Lovett DH. 37.  1997. The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein. PNAS 94:508–13 [Google Scholar]
  38. Werman A, Werman-Venkert R, White R, Lee JK, Werman B. 38.  et al. 2004. The precursor form of IL-1α is an intracrine proinflammatory activator of transcription. PNAS 101:2434–39 [Google Scholar]
  39. Ali S, Mohs A, Thomas M, Klare J, Ross R. 39.  et al. 2011. The dual function cytokine IL-33 interacts with the transcription factor NF-κB to dampen NF-κB-stimulated gene transcription. J. Immunol. 187:1609–16 [Google Scholar]
  40. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A. 40.  et al. 1995. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378:88–91 [Google Scholar]
  41. Dinarello CA. 41.  2000. Interleukin-18, a proinflammatory cytokine. Eur. Cytokine Netw. 11:483–86 [Google Scholar]
  42. Gatti S, Beck J, Fantuzzi G, Bartfai T, Dinarello CA. 42.  2002. Effect of interleukin-18 on mouse core body temperature. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282:R702–9 [Google Scholar]
  43. Stuyt RJL, Netea MG, Verschueren I, Dinarello CA, Kullberg BJ, van der Meer JWM. 43.  2005. Interleukin-18 does not modulate the acute-phase response. J. Endotoxin Res. 11:85–88 [Google Scholar]
  44. Reznikov LL, Kim SH, Westcott JY, Frishman J, Fantuzzi G. 44.  et al. 2000. IL-18 binding protein increases spontaneous and IL-1-induced prostaglandin production via inhibition of IFN-γ. PNAS 97:2174–79 [Google Scholar]
  45. Lee JK, Kim SH, Lewis EC, Azam T, Reznikov LL, Dinarello CA. 45.  2004. Differences in signaling pathways by IL-1β and IL-18. PNAS 101:8815–20 [Google Scholar]
  46. Dorresteijn MJ, Pickkers P, Netea MG, Van der Hoeven JG. 46.  2005. IFN-γ is not induced through increased plasma concentrations of interleukin-12/interleukin-18 during human endotoxemia. Eur. Cytokine Netw. 16:191–93 [Google Scholar]
  47. van de Veerdonk FL, Wever PC, Hermans MHA, Fijnheer R, Joosten LAB. 47.  et al. 2012. IL-18 serum concentration is markedly elevated in acute EBV infection and can serve as a marker for disease severity. J. Infect. Dis. 206:197–201 [Google Scholar]
  48. ten Oever J, Tromp M, Bleeker-Rovers CP, Joosten LAB, Netea MG. 48.  et al. 2012. Combination of biomarkers for the discrimination between bacterial and viral lower respiratory tract infections. J. Infect. 65:490–95 [Google Scholar]
  49. Priori R, Barone F, Alessandri C, Colafrancesco S, McInnes IB. 49.  et al. 2011. Markedly increased IL-18 liver expression in adult-onset Still's disease-related hepatitis. Rheumatology 50:776–80 [Google Scholar]
  50. Priori R, Colafrancesco S, Alessandri C, Minniti A, Perricone C. 50.  et al. 2014. Interleukin 18: a biomarker for differential diagnosis between adult-onset Still's disease and sepsis. J. Rheumatol. 41:1118–23 [Google Scholar]
  51. Dinarello CA. 51.  2007. Interleukin-18 and the pathogenesis of inflammatory diseases. Semin. Nephrol. 27:98–114 [Google Scholar]
  52. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. 52.  2001. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 12:53–72 [Google Scholar]
  53. Mailliard RB, Alber SM, Shen H, Watkins SC, Kirkwood JM. 53.  et al. 2005. IL-18–induced CD83+CCR7+ NK helper cells. J. Exp. Med. 202:941–53 [Google Scholar]
  54. Bellora F, Castriconi R, Doni A, Cantoni C, Moretta L. 54.  et al. 2012. M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages. Eur. J. Immunol. 42:1618–26 [Google Scholar]
  55. Tsutsui H, Matsui K, Okamura H, Nakanishi K. 55.  2000. Pathophysiological roles of interleukin-18 in inflammatory liver diseases. Immunol. Rev. 174:192–209 [Google Scholar]
  56. Mazodier K, Marin V, Novick D, Farnarier C, Robitail S. 56.  et al. 2005. Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome. Blood 106:3483–89 [Google Scholar]
  57. Puren AJ, Fantuzzi G, Dinarello CA. 57.  1999. Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1β are differentially regulated in human blood mononuclear cells and mouse spleen cells. PNAS 96:2256–61 [Google Scholar]
  58. Netea MG, Joosten LAB, Lewis E, Jensen DR, Voshol PJ. 58.  et al. 2006. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat. Med. 12:650–56 [Google Scholar]
  59. Zorrilla EP, Sanchez-Alavez M, Sugama S, Brennan M, Fernandez R. 59.  et al. 2007. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. PNAS 104:11097–102 [Google Scholar]
  60. Dinarello CA, Novick D, Kim S, Kaplanski G. 60.  2013. Interleukin-18 and IL-18 binding protein. Front. Immunol. 4:289 [Google Scholar]
  61. Sharma S, Kulk N, Nold MF, Gräf R, Kim SH. 61.  et al. 2008. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. J. Immunol. 180:5477–82 [Google Scholar]
  62. Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. 62.  2010. IL-37 is a fundamental inhibitor of innate immunity. Nat. Immunol. 11:1014–22 [Google Scholar]
  63. McNamee EN, Masterson JC, Jedlicka P, McManus M, Grenz A. 63.  et al. 2011. Interleukin 37 expression protects mice from colitis. PNAS 108:16711–16 [Google Scholar]
  64. Dinarello C, Arend W, Sims J, Smith D, Blumberg H. 64.  et al. 2010. IL-1 family nomenclature. Nat. Immunol. 11:973 [Google Scholar]
  65. Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE. 65.  2004. Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-κB and MAPKs. J. Biol. Chem. 279:13677–88 [Google Scholar]
  66. Magne D, Palmer G, Barton JL, Mézin F, Talabot-Ayer D. 66.  et al. 2006. The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes. Arthritis Res. Ther. 8:R80 [Google Scholar]
  67. Chustz RT, Nagarkar DR, Poposki JA, Favoreto S Jr, Avila PC. 67.  et al. 2011. Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 45:145–53 [Google Scholar]
  68. Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE. 68.  2000. Four new members expand the interleukin-1 superfamily. J. Biol. Chem. 275:1169–75 [Google Scholar]
  69. Barksby HE, Nile CJ, Jaedicke KM, Taylor JJ, Preshaw PM. 69.  2009. Differential expression of immunoregulatory genes in monocytes in response to Porphyromonas gingivalis and Escherichia coli lipopolysaccharide. Clin. Exp. Immunol. 156:479–87 [Google Scholar]
  70. Guo L, Wei G, Zhu J, Liao W, Leonard WJ. 70.  et al. 2009. IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. PNAS 106:13463–68 [Google Scholar]
  71. Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M. 71.  et al. 2011. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) activity. J. Biol. Chem. 286:42594–602 [Google Scholar]
  72. Carrier Y, Ma HL, Ramon HE, Napierata L, Small C. 72.  et al. 2011. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J. Invest. Dermatol. 131:2428–37 [Google Scholar]
  73. Yang J, Meyer M, Muller AK, Bohm F, Grose R. 73.  et al. 2010. Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis. J. Cell Biol. 188:935–52 [Google Scholar]
  74. Franzke CW, Cobzaru C, Triantafyllopoulou A, Löffek S, Horiuchi K. 74.  et al. 2012. Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation. J. Exp. Med. 209:1105–19 [Google Scholar]
  75. Blumberg H, Dinh H, Trueblood ES, Pretorius J, Kugler D. 75.  et al. 2007. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J. Exp. Med. 204:2603–14 [Google Scholar]
  76. Vos JB, van Sterkenburg MA, Rabe KF, Schalkwijk J, Hiemstra PS, Datson NA. 76.  2005. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense. Physiol. Genomics 21:324–36 [Google Scholar]
  77. Dunn EF, Gay NJ, Bristow AF, Gearing DP, O'Neill LA, Pei XY. 77.  2003. High-resolution structure of murine interleukin 1 homologue IL-1F5 reveals unique loop conformations for receptor binding specificity. Biochemistry 42:10938–44 [Google Scholar]
  78. Debets R, Timans JC, Homey B, Zurawski S, Sana TR. 78.  et al. 2001. Two novel IL-1 family members, IL-1δ and IL-1ϵ, function as an antagonist and agonist of NF-κB activation through the orphan IL-1 receptor-related protein 2. J. Immunol. 167:1440–46 [Google Scholar]
  79. Blumberg H, Dinh H, Dean C Jr, Trueblood ES, Bailey K. 79.  et al. 2010. IL-1RL2 and its ligands contribute to the cytokine network in psoriasis. J. Immunol. 185:4354–62 [Google Scholar]
  80. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY. 80.  et al. 2011. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N. Engl. J. Med. 365:620–28 [Google Scholar]
  81. Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH. 81.  et al. 2011. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am. J. Hum. Genet. 89:432–37 [Google Scholar]
  82. Sugiura K, Takeichi T, Kono M, Ogawa Y, Shimoyama Y. 82.  et al. 2012. A novel IL36RN/IL1F5 homozygous nonsense mutation, p.Arg10X, in a Japanese patient with adult-onset generalized pustular psoriasis. Br. J. Dermatol. 167:699–701 [Google Scholar]
  83. Farooq M, Nakai H, Fujimoto A, Fujikawa H, Matsuyama A. 83.  et al. 2013. Mutation analysis of the IL36RN gene in 14 Japanese patients with generalized pustular psoriasis. Hum. Mutat. 34:176–83 [Google Scholar]
  84. Bensen JT, Dawson PA, Mychaleckyj JC, Bowden DW. 84.  2001. Identification of a novel human cytokine gene in the interleukin gene cluster on chromosome 2q12-14. J. Interferon Cytokine Res. 21:899–904 [Google Scholar]
  85. Lin H, Ho AS, Haley-Vicente D, Zhang J, Bernal-Fussell J. 85.  et al. 2001. Cloning and characterization of IL-1HY2, a novel interleukin-1 family member. J. Biol. Chem. 276:20597–602 [Google Scholar]
  86. Rahman P, Sun S, Peddle L, Snelgrove T, Melay W. 86.  et al. 2006. Association between the interleukin-1 family gene cluster and psoriatic arthritis. Arthritis Rheumatol. 54:2321–25 [Google Scholar]
  87. Chou CT, Timms AE, Wei JC, Tsai WC, Wordsworth BP, Brown MA. 87.  2006. Replication of association of IL1 gene complex members with ankylosing spondylitis in Taiwanese Chinese. Ann. Rheum. Dis. 65:1106–9 [Google Scholar]
  88. Guo ZS, Li C, Lin ZM, Huang JX, Wei QJ. 88.  et al. 2010. Association of IL-1 gene complex members with ankylosing spondylitis in Chinese Han population. Int. J. Immunogenetics 37:33–37 [Google Scholar]
  89. Dehghan A, Dupuis J, Barbalic M, Bis JC, Eiriksdottir G. 89.  et al. 2011. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 123:731–38 [Google Scholar]
  90. van de Veerdonk FL, Stoeckman AK, Wu G, Boeckermann AN, Azam T. 90.  et al. 2012. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. PNAS 109:3001–5 [Google Scholar]
  91. Wilson KP, Black JF, Thomson JA, Kim EE, Griffith JP. 91.  et al. 1994. Structure and mechanism of interleukin-1β converting enzyme. Nature 370:270–75 [Google Scholar]
  92. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K. 92.  et al. 1992. Molecular cloning of the interleukin-1 beta converting enzyme. Science 256:97–100 [Google Scholar]
  93. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD. 93.  et al. 1992. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 356:768–74 [Google Scholar]
  94. Martinon F, Burns K, Tschopp J. 94.  2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417–26 [Google Scholar]
  95. Martinon F, Agostini L, Meylan E, Tschopp J. 95.  2004. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr. Biol. 14:1929–34 [Google Scholar]
  96. Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S. 96.  et al. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479:117–21 [Google Scholar]
  97. Lamkanfi M, Dixit VM. 97.  2014. Mechanisms and functions of inflammasomes. Cell 157:1013–22 [Google Scholar]
  98. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA. 98.  et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–57 [Google Scholar]
  99. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP. 99.  et al. 2014. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–59 [Google Scholar]
  100. Eisenbarth SC, Williams A, Colegio OR, Meng H, Strowig T. 100.  et al. 2012. NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells. Nature 484:510–13 [Google Scholar]
  101. Kanneganti TD, Özören N, Body-Malapel M, Amer A, Park JH. 101.  et al. 2006. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440:233–36 [Google Scholar]
  102. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K. 102.  et al. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–32 [Google Scholar]
  103. Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. 103.  2008. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122–26 [Google Scholar]
  104. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. 104.  2008. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674–77 [Google Scholar]
  105. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G. 105.  et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–61 [Google Scholar]
  106. Arlehamn CSL, Pétrilli V, Gross O, Tschopp J, Evans TJ. 106.  2010. The role of potassium in inflammasome activation by bacteria. J. Biol. Chem. 285:10508–18 [Google Scholar]
  107. Misawa T, Takahama M, Kozaki T, Lee H, Zou J. 107.  et al. 2013. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14:454–60 [Google Scholar]
  108. Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN. 108.  2013. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 153:348–61 [Google Scholar]
  109. Zhou R, Yazdi AS, Menu P, Tschopp J. 109.  2011. A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–25 [Google Scholar]
  110. Iyer SS, He Q, Janczy JR, Elliott EI, Zhong Z. 110.  et al. 2013. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39:311–23 [Google Scholar]
  111. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T. 111.  et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12:222–30 [Google Scholar]
  112. van de Veerdonk FL, Smeekens SP, Joosten LAB, Kullberg BJ, Dinarello CA. 112.  et al. 2010. Reactive oxygen species–independent activation of the IL-1β inflammasome in cells from patients with chronic granulomatous disease. PNAS 107:3030–33 [Google Scholar]
  113. Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. 113.  2010. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood 116:1570–73 [Google Scholar]
  114. Meissner F, Molawi K, Zychlinsky A. 114.  2008. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat. Immunol. 9:866–72 [Google Scholar]
  115. Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E. 115.  et al. 2007. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol. Cell 25:713–24 [Google Scholar]
  116. Hsu LC, Ali SR, McGillivray S, Tseng PH, Mariathasan S. 116.  et al. 2008. A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide. PNAS 105:7803–8 [Google Scholar]
  117. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G. 117.  et al. 2007. NALP1 in vitiligo-associated multiple autoimmune disease. N. Engl. J. Med. 356:1216–25 [Google Scholar]
  118. Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Özören N. 118.  et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat. Immunol. 7:576–82 [Google Scholar]
  119. Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW. 119.  et al. 2006. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nat. Immunol. 7:569–75 [Google Scholar]
  120. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G. 120.  et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18 [Google Scholar]
  121. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. 121.  2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509–13 [Google Scholar]
  122. Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S. 122.  et al. 2010. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11:385–93 [Google Scholar]
  123. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM. 123.  et al. 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505:509–14 [Google Scholar]
  124. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G. 124.  et al. 2014. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 343:428–32 [Google Scholar]
  125. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau A. 125.  1988. Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6. J. Immunol. 140:1534–41 [Google Scholar]
  126. Fantuzzi G, Ku G, Harding MW, Livingston DJ, Sipe JD. 126.  et al. 1997. Response to local inflammation of IL-1 beta-converting enzyme-deficient mice. J. Immunol. 158:1818–24 [Google Scholar]
  127. Coeshott C, Ohnemus C, Pilyavskaya A, Ross S, Wieczorek M. 127.  et al. 1999. Converting enzyme-independent release of tumor necrosis factor α and IL-1β from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. PNAS 96:6261–66 [Google Scholar]
  128. Sugawara S, Uehara A, Nochi T, Yamaguchi T, Ueda H. 128.  et al. 2001. Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells. J. Immunol. 167:6568–75 [Google Scholar]
  129. Herzog C, Haun RS, Kaushal V, Mayeux PR, Shah SV, Kaushal GP. 129.  2009. Meprin A and meprin α generate biologically functional IL-1β from pro-IL-1β. Biochem. Biophys. Res. Commun. 379:904–8 [Google Scholar]
  130. Omoto Y, Tokime K, Yamanaka K, Habe K, Morioka T. 130.  et al. 2006. Human mast cell chymase cleaves pro-IL-18 and generates a novel and biologically active IL-18 fragment. J. Immunol. 177:8315–19 [Google Scholar]
  131. Omoto Y, Yamanaka K, Tokime K, Kitano S, Kakeda M. 131.  et al. 2010. Granzyme B is a novel interleukin-18 converting enzyme. J. Dermatol. Sci. 59:129–35 [Google Scholar]
  132. Banerjee S, Bond JS. 132.  2008. Prointerleukin-18 is activated by meprin β in vitro and in vivo in intestinal inflammation. J. Biol. Chem. 283:31371–77 [Google Scholar]
  133. Bae S, Kang T, Hong J, Lee S, Choi J. 133.  et al. 2012. Contradictory functions (activation/termination) of neutrophil proteinase 3 enzyme (PR3) in interleukin-33 biological activity. J. Biol. Chem. 287:8205–13 [Google Scholar]
  134. Kullberg BJ, Van ‘t Wout JW, Van Furth R. 134.  1990. Role of granulocytes in enhanced host resistance to Candida albicans induced by recombinant interleukin-1. Infect. Immun. 58:3319–24 [Google Scholar]
  135. Vonk AG, Netea MG, van der Meer JWM, Kullberg BJ. 135.  2006. Host defence against disseminated Candida albicans infection and implications for antifungal immunotherapy. Expert Opin. Biol. Ther. 6:891–903 [Google Scholar]
  136. Mencacci A, Bacci A, Cenci E, Montagnoli C, Fiorucci S. 136.  et al. 2000. Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1-deficient mice. Infect. Immun. 68:5126–31 [Google Scholar]
  137. Joosten LAB, Netea MG, Fantuzzi G, Koenders MI, Helsen MMA. 137.  et al. 2009. Inflammatory arthritis in caspase 1 gene–deficient mice: contribution of proteinase 3 to caspase 1–independent production of bioactive interleukin-1β. Arthritis Rheumatol. 60:3651–62 [Google Scholar]
  138. van de Veerdonk FL, Joosten LAB, Shaw PJ, Smeekens SP, Malireddi RKS. 138.  et al. 2011. The inflammasome drives protective Th1 and Th17 cellular responses in disseminated candidiasis. Eur. J. Immunol. 41:2260–68 [Google Scholar]
  139. Guma M, Ronacher L, Liu-Bryan R, Takai S, Karin M, Corr M. 139.  2009. Caspase 1–independent activation of interleukin-1β in neutrophil-predominant inflammation. Arthritis Rheumatol. 60:3642–50 [Google Scholar]
  140. Cassel SL, Janczy JR, Bing X, Wilson SP, Olivier AK. 140.  et al. 2014. Inflammasome-independent IL-1β mediates autoinflammatory disease in Pstpip2-deficient mice. PNAS 111:1072–77 [Google Scholar]
  141. Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M. 141.  et al. 2014. Critical role for inflammasome-independent IL-1β production in osteomyelitis. PNAS 111:1066–71 [Google Scholar]
  142. Berende A, Oosting M, Kullberg BJ, Netea MG, Joosten LAB. 142.  2010. Activation of innate host defense mechanisms by Borrelia. Eur. Cytokine Netw. 21:7–18 [Google Scholar]
  143. Bagby GC Jr, Dinarello CA, Wallace P, Wagner C, Hefeneider S, McCall E. 143.  1986. Interleukin 1 stimulates granulocyte macrophage colony-stimulating activity release by vascular endothelial cells. J. Clin. Invest. 78:1316–23 [Google Scholar]
  144. Dinarello CA, Ikejima T, Warner SJC, Orencole SF, Lonnemann G. 144.  et al. 1987. Interleukin 1 induces interleukin 1. I. Induction of interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J. Immunol. 139:1902–10 [Google Scholar]
  145. Netea MG, Nold-Petry CA, Nold MF, Joosten LAB, Opitz B. 145.  et al. 2009. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 113:2324–35 [Google Scholar]
  146. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A. 146.  et al. 2006. The P2X7 receptor: a key player in IL-1 processing and release. J. Immunol. 176:3877–83 [Google Scholar]
  147. Elssner A, Duncan M, Gavrilin M, Wewers MD. 147.  2004. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1β processing and release. J. Immunol. 172:4987–94 [Google Scholar]
  148. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K. 148.  et al. 2009. Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183:787–91 [Google Scholar]
  149. Guma M, Kashiwakura J, Crain B, Kawakami Y, Beutler B. 149.  et al. 2010. JNK1 controls mast cell degranulation and IL-1β production in inflammatory arthritis. PNAS 107:22122–27 [Google Scholar]
  150. Nakamura Y, Franchi L, Kambe N, Meng G, Strober W, Núñez G. 150.  2012. Critical role for mast cells in interleukin-1β-driven skin inflammation associated with an activating mutation in the Nlrp3 protein. Immunity 37:85–95 [Google Scholar]
  151. Cho JS, Guo Y, Ramos RI, Hebroni F, Plaisier SB. 151.  et al. 2012. Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLOS Pathog. 8:e1003047 [Google Scholar]
  152. Schreiber A, Pham CTN, Hu Y, Schneider W, Luft FC, Kettritz R. 152.  2012. Neutrophil serine proteases promote IL-1β generation and injury in necrotizing crescentic glomerulonephritis. J. Am. Soc. Nephrol. 23:470–82 [Google Scholar]
  153. Hanamsagar R, Torres V, Kielian T. 153.  2011. Inflammasome activation and IL-1β/IL-18 processing are influenced by distinct pathways in microglia. J. Neurochem. 119:736–48 [Google Scholar]
  154. Boyden ED, Dietrich WF. 154.  2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat. Genet. 38:240–44 [Google Scholar]
  155. Özören N, Masumoto J, Franchi L, Kanneganti TD, Body-Malapel M. 155.  et al. 2006. Distinct roles of TLR2 and the adaptor ASC in IL-1β/IL-18 secretion in response to Listeria monocytogenes. J. Immunol. 176:4337–42 [Google Scholar]
  156. Warren SE, Mao DP, Rodriguez AE, Miao EA, Aderem A. 156.  2008. Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J. Immunol. 180:7558–64 [Google Scholar]
  157. Franchi L, Kanneganti TD, Dubyak GR, Núñez G. 157.  2007. Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. J. Biol. Chem. 282:18810–18 [Google Scholar]
  158. Mariathasan S, Newton K, Monack DM, Vucic D, French DM. 158.  et al. 2004. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213–18 [Google Scholar]
  159. Amer A, Franchi L, Kanneganti TD, Body-Malapel M, Özören N. 159.  et al. 2006. Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J. Biol. Chem. 281:35217–23 [Google Scholar]
  160. Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA. 160.  2007. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 204:3235–45 [Google Scholar]
  161. Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M. 161.  et al. 2007. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLOS Pathog. 3:e111 [Google Scholar]
  162. Mariathasan S, Weiss DS, Dixit VM, Monack DM. 162.  2005. Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. J. Exp. Med. 202:1043–49 [Google Scholar]
  163. Ren T, Zamboni DS, Roy CR, Dietrich WF, Vance RE. 163.  2006. Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLOS Pathog. 2:e18 [Google Scholar]
  164. Raupach B, Peuschel SK, Monack DM, Zychlinsky A. 164.  2006. Caspase-1-mediated activation of interleukin-1β (IL-1β) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect. Immun. 74:4922–26 [Google Scholar]
  165. Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J. 165.  et al. 2006. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J. Exp. Med. 203:1407–12 [Google Scholar]
  166. Miller LS, Pietras EM, Uricchio LH, Hirano K, Rao S. 166.  et al. 2007. Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo. J. Immunol. 179:6933–42 [Google Scholar]
  167. Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. 167.  2009. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med. 206:79–87 [Google Scholar]
  168. Gross O, Poeck H, Bscheider M, Dostert C, Hannesschläger N. 168.  et al. 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459:433–36 [Google Scholar]
  169. Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA. 169.  et al. 2009. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 5:487–97 [Google Scholar]
  170. Hasegawa M, Imamura R, Kinoshita T, Matsumoto N, Masumoto J. 170.  et al. 2005. ASC-mediated NF-κB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP. J. Biol. Chem. 280:15122–30 [Google Scholar]
  171. Shigeoka AA, Mueller JL, Kambo A, Mathison JC, King AJ. 171.  et al. 2010. An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. J. Immunol. 185:6277–85 [Google Scholar]
  172. de Veerdonk FL, Joosten LAB, Devesa I, Mora-Montes HM, Kanneganti TD. 172.  van et al. 2009. Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans. J. Infect. Dis. 199:1087–96 [Google Scholar]
  173. Beauséjour A, Grenier D, Goulet JP, Deslauriers N. 173.  1998. Proteolytic activation of the interleukin-1β precursor by Candida albicans. Infect. Immun. 66:676–81 [Google Scholar]
  174. Gottar M, Gobert V, Matskevich AA, Reichhart JM, Wang C. 174.  et al. 2006. Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell 127:1425–37 [Google Scholar]
  175. Black RA, Kronheim SR, Cantrell M, Deeley MC, March CJ. 175.  et al. 1988. Generation of biologically active interleukin-1β by proteolytic cleavage of the inactive precursor. J. Biol. Chem. 263:9437–42 [Google Scholar]
  176. Zhang Z, Wang L, Seydel KB, Li E, Ankri S. 176.  et al. 2000. Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting enzyme (ICE) activity cause intestinal inflammation and tissue damage in amoebiasis. Mol. Microbiol. 37:542–48 [Google Scholar]
  177. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ. 177.  et al. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin-β converting enzyme. Science 267:2000–3 [Google Scholar]
  178. Li P, Allen H, Banerjee S, Franklin S, Herzog L. 178.  et al. 1995. Mice deficient in IL-1β-converting enzyme are defective in production of nature IL-1β and resistant to endotoxic shock. Cell 80:401–11 [Google Scholar]
  179. Lu H, Shen C, Brunham RC. 179.  2000. Chlamydia trachomatis infection of epithelial cells induces the activation of caspase-1 and release of mature IL-18. J. Immunol. 165:1463–69 [Google Scholar]
  180. Cheng W, Shivshankar P, Li Z, Chen L, Yeh IT, Zhong G. 180.  2008. Caspase-1 contributes to Chlamydia trachomatis-induced upper urogenital tract inflammatory pathologies without affecting the course of infection. Infect. Immun. 76:515–22 [Google Scholar]
  181. Bellocchio S, Montagnoli C, Bozza S, Gaziano R, Rossi G. 181.  et al. 2004. The contribution of Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172:3059–69 [Google Scholar]
  182. Karmakar M, Sun Y, Hise AG, Rietsch A, Pearlman E. 182.  2012. Cutting edge: IL-1β processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and caspase-1. J. Immunol. 189:4231–35 [Google Scholar]
  183. Juffermans NP, Florquin S, Camoglio L, Verbon A, Kolk AH. 183.  et al. 2000. Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis. J. Infect. Dis. 182:902–8 [Google Scholar]
  184. McElvania Tekippe E, Allen IC, Hulseberg PD, Sullivan JT, McCann JR. 184.  et al. 2010. Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLOS ONE 5:e12320 [Google Scholar]
  185. Dorhoi A, Nouailles G, Jorg S, Hagens K, Heinemann E. 185.  et al. 2012. Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis. Eur. J. Immunol. 42:374–84 [Google Scholar]
  186. Eklund D, Welin A, Andersson H, Verma D, Soderkvist P. 186.  et al. 2014. Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis. J. Infect. Dis. 209:749–53 [Google Scholar]
  187. Aksentijevich I, Kastner DL. 187.  2011. Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat. Rev. Rheumatol. 7:469–78 [Google Scholar]
  188. Masters SL, Simon A, Aksentijevich I, Kastner DL. 188.  2009. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu. Rev. Immunol. 27:621–68 [Google Scholar]
  189. Chae JJ, Cho YH, Lee GS, Cheng J, Liu PP. 189.  et al. 2011. Gain-of-function pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in mice. Immunity 34:755–68 [Google Scholar]
  190. Omenetti A, Carta S, Delfino L, Martini A, Gattorno M, Rubartelli A. 190.  2014. Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation with MEFV genotype. Ann. Rheum. Dis. 73:462–69 [Google Scholar]
  191. Soriano A, Verecchia E, Afeltra A, Landolfi R, Manna R. 191.  2013. IL-1β biological treatment of familial Mediterranean fever. Clin. Rev. Allergy Immunol. 45:117–30 [Google Scholar]
  192. Dinarello CA. 192.  2014. Interleukin-1α neutralisation in patients with cancer. Lancet Oncol. 15:552–53 [Google Scholar]
  193. Masters SL, Lobito AA, Chae J, Kastner DL. 193.  2006. Recent advances in the molecular pathogenesis of hereditary recurrent fevers. Curr. Opin. Allergy Clin. Immunol. 6:428–33 [Google Scholar]
  194. Simon A, Bodar EJ, van der Hilst JCH, van der Meer JWM, Fiselier TJW. 194.  et al. 2004. Beneficial response to interleukin 1 receptor antagonist in traps. Am. J. Med. 117:208–10 [Google Scholar]
  195. de Koning HD, Bodar EJ, Simon A, van der Hilst JCH, Netea MG, van der Meer JWM. 195.  2006. Beneficial response to anakinra and thalidomide in Schnitzler's syndrome. Ann. Rheum. Dis. 65:542–44 [Google Scholar]
  196. Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J. 196.  et al. 2009. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N. Engl. J. Med. 360:2426–37 [Google Scholar]
  197. Rossi-Semerano L, Piram M, Chiaverini C, De Ricaud D, Smahi A, Kone-Paut I. 197.  2013. First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics 132:e1043–47 [Google Scholar]
  198. Tauber M, Viguier M, Alimova E, Petit A, Lioté F. 198.  et al. 2014. Partial clinical response to anakinra in severe palmoplantar pustular psoriasis. Br. J. Dermatol. 171:646–49 [Google Scholar]
  199. So A, De Smedt T, Revaz S, Tschopp J. 199.  2007. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res. Ther. 9:R28 [Google Scholar]
  200. Edwards NL, So A. 200.  2014. Emerging therapies for gout. Rheum. Dis. Clin. North Am. 40:375–87 [Google Scholar]
  201. Joosten LAB, Netea MG, Mylona E, Koenders MI, Malireddi RKS. 201.  et al. 2010. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal–induced gouty arthritis. Arthritis Rheumatol. 62:3237–48 [Google Scholar]
  202. Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C. 202.  et al. 2010. Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis. J. Biol. Chem. 285:12454–62 [Google Scholar]
  203. Croker BA, Lewis RS, Babon JJ, Mintern JD, Jenne DE. 203.  et al. 2011. Neutrophils require SHP1 to regulate IL-1β production and prevent inflammatory skin disease. J. Immunol. 186:1131–39 [Google Scholar]
  204. Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S. 204.  et al. 2013. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. PNAS 110:2952–56 [Google Scholar]
  205. Greten FR, Arkan MC, Bollrath J, Hsu LC, Goode J. 205.  et al. 2007. NF-κB is a negative regulator of IL-1β secretion as revealed by genetic and pharmacological inhibition of IKKβ. Cell 130:918–31 [Google Scholar]
  206. Gattorno M, Piccini A, Lasiglie D, Tassi S, Brisca G. 206.  et al. 2008. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheumatol. 58:1505–15 [Google Scholar]
  207. de Luca A, Smeekens SP, Casagrande A, Iannitti R, Conway KL. 207.  et al. 2014. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. PNAS 111:3526–31 [Google Scholar]
  208. Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI. 208.  et al. 2002. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest. 110:851–60 [Google Scholar]
  209. Pope RM, Tschopp J. 209.  2007. The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheumatol. 56:3183–88 [Google Scholar]
  210. Popa-Nita O, Rollet-Labelle E, Thibault N, Gilbert C, Bourgoin SG, Naccache PH. 210.  2007. Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase. J. Leukoc. Biol. 82:763–73 [Google Scholar]
  211. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. 211.  2001. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet. 29:301–5 [Google Scholar]
  212. Fantuzzi G, Dinarello CA. 212.  1996. The inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine-related knock-out mice. J. Leukoc. Biol. 59:489–93 [Google Scholar]
  213. Netea MG, Fantuzzi G, Kullberg BJ, Stuyt RJL, Pulido EJ. 213.  et al. 2000. Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia. J. Immunol. 164:2644–49 [Google Scholar]
  214. Hochholzer P, Lipford GB, Wagner H, Pfeffer K, Heeg K. 214.  2000. Role of interleukin-18 (IL-18) during lethal shock: decreased lipopolysaccharide sensitivity but normal superantigen reaction in IL-18-deficient mice. Infect. Immun. 68:3502–8 [Google Scholar]
  215. Barreiro LB, Quintana-Murci L. 215.  2010. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat. Rev. Genet. 11:17–30 [Google Scholar]
  216. Sarkar A, Hall MW, Exline M, Hart J, Knatz N. 216.  et al. 2006. Caspase-1 regulates Escherichia coli sepsis and splenic B cell apoptosis independently of interleukin-1β and interleukin-18. Am. J. Respir. Crit. Care Med. 174:1003–10 [Google Scholar]
  217. Joshi VD, Kalvakolanu DV, Hebel JR, Hasday JD, Cross AS. 217.  2002. Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia. Infect. Immun. 70:6896–903 [Google Scholar]
  218. Sansonetti PJ, Phalipon A, Arondel J, Thirumalai K, Banerjee S. 218.  et al. 2000. Caspase-1 activation of IL-1β and IL-18 are essential for Shigella flexneri--induced inflammation. Immunity 12:581–90 [Google Scholar]
  219. Netea MG, Stuyt RJL, Kim SH, Van der Meer JWM, Kullberg BJ, Dinarello CA. 219.  2002. The role of endogenous interleukin (IL)–18, IL-12, IL-1β, and tumor necrosis factor–α in the production of interferon-γ induced by Candida albicans in human whole-blood cultures. J. Infect. Dis. 185:963–70 [Google Scholar]
  220. Miller LS, Pietras EM, Uricchio LH, Hirano K, Rao S. 220.  et al. 2007. Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo. J. Immunol. 179:6933–42 [Google Scholar]
  221. Wei XQ, Leung BP, Niedbala W, Piedrafita D, Feng GJ. 221.  et al. 1999. Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. J. Immunol. 163:2821–28 [Google Scholar]
  222. Barankin B, DeKoven J. 222.  2002. Psychosocial effect of common skin diseases. Can. Fam. Physician 48:712–16 [Google Scholar]
  223. Zheng H, Fletcher D, Kozak W, Jiang M, Hofmann KJ. 223.  et al. 1995. Resistance to fever induction and impaired acute-phase response in interleukin-1β-deficient mice. Immunity 3:9–19 [Google Scholar]
  224. Lochner M, Kastenmuller K, Neuenhahn M, Weighardt H, Busch DH. 224.  et al. 2008. Decreased susceptibility of mice to infection with Listeria monocytogenes in the absence of interleukin-18. Infect. Immun. 76:3881–90 [Google Scholar]
  225. Tsuji NM, Tsutsui H, Seki E, Kuida K, Okamura H. 225.  et al. 2004. Roles of caspase-1 in Listeria infection in mice. Int. Immunol. 16:335–43 [Google Scholar]
  226. Case CL, Shin S, Roy CR. 226.  2009. Asc and Ipaf inflammasomes direct distinct pathways for caspase-1 activation in response to Legionella pneumophila. Infect. Immun. 77:1981–91 [Google Scholar]
  227. Gregory SM, Davis BK, West JA, Taxman DJ, Matsuzawa S. 227.  et al. 2011. Discovery of a viral NLR homolog that inhibits the inflammasome. Science 331:330–34 [Google Scholar]
  228. Van Der Sluijs KF, Van Elden LJR, Arens R, Nijhuis M, Schuurman R. 228.  et al. 2005. Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus. Immunology 114:112–20 [Google Scholar]
  229. Liu B, Mori I, Hossain MJ, Dong L, Takeda K, Kimura Y. 229.  2004. Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity. J. Gen. Virol. 85:423–28 [Google Scholar]

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