The Inflammasome NLRs in immunity, inflammation, and associated diseases

Annual Review of Immunology

Volumn 29, Issue , 2011, Pages 707-735

  Davis, Beckley K ^a   Wen, Haitao ^a   Ting, Jenny P Y ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

cancer; caspase 1; IL 1 ; innate immunity; metabolic diseases

Indexed keywords

INFLAMMASOME; INTERLEUKIN 18; INTERLEUKIN 1BETA;

ARTICLE; CARCINOGENESIS; CYTOKINE RELEASE; ENTERITIS; ENZYME ACTIVATION; HUMAN; INNATE IMMUNITY; LIVER INJURY; METABOLIC DISORDER; NONHUMAN; NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; INFLAMMASOMES; INFLAMMATION; INFLAMMATION MEDIATORS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; METABOLIC DISEASES; NEOPLASMS;

EID: 79953046719     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-031210-101405     Document Type: Article

References (175)

1. Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, et al. 2008. The NLR gene family: a standard nomenclature. Immunity 28:285-87. (Pubitemid 351350631)
2. Ting JP, Davis BK. 2005. CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu. Rev. Immunol. 23:387-414. (Pubitemid 40563175)
3. Ausubel FM. 2005. Are innate immune signaling pathways in plants and animals conserved? Nat. Immunol. 6:973-79. (Pubitemid 41486181)
4. Rast JP, Smith LC, Loza-Coll M, Hibino T, Litman GW. 2006. Genomic insights into the immune system of the sea urchin. Science 314:952-56. (Pubitemid 44749931)
5. Schroder K, Tschopp J. 2010. The inflammasomes. Cell 140:821-32.
6. Martinon F, Burns K, Tschopp J. 2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417-26. (Pubitemid 35007355)
7. Keller M, Ruegg A, Werner S, Beer HD. 2008. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132:818-31. (Pubitemid 351312798)
8. Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, et al. 2007. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol. Cell 25:713-24. (Pubitemid 46341921)
9. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. 2004. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20:319-25. (Pubitemid 38388233)
10. Grenier JM, Wang L, Manji GA, Huang WJ, Al-Garawi A, et al. 2002. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-κB and caspase-1. FEBS Lett. 530:73-78. (Pubitemid 35248189)
11. Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, et al. 2002. PYPAF7, a novel PYRINcontaining Apaf1-like protein that regulates activation of NF-κB and caspase-1-dependent cytokine processing. J. Biol. Chem. 277:29874-80.
12. 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. 276:28309-13.
13. O'Connor W Jr, Harton JA, Zhu X, Linhoff MW, Ting JP. 2003. Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties. J. Immunol. 171:6329-33. (Pubitemid 37532057)
14. 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. 29:301-5. (Pubitemid 33096455)
15. Allen IC, ScullMA, MooreCB, Holl EK, McElvania-TeKippe E, et al. 2009. TheNLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30:556-65.
16. Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J. 2007. A crucial function of SGT1 andHSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat. Immunol. 8:497-503. (Pubitemid 46605918)
17. Hahn JS. 2005. Regulation of Nod1 by Hsp90 chaperone complex. FEBS Lett. 579:4513-19.
18. Arthur JC, Lich JD, Aziz RK, Kotb M, Ting JP. 2007. Heat shock protein 90 associates with monarch-1 and regulates its ability to promote degradation of NF-κB-inducing kinase. J. Immunol. 179:6291-96.
19. HoffmanHM, Wanderer AA. 2010. Inflammasome and IL-1β-mediated disorders. Curr. Allergy Asthma Rep. 10:229-35.
20. Masters SL, Simon A, Aksentijevich I, KastnerDL. 2009. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu. Rev. Immunol. 27:621-68.
21. Duncan JA, Bergstralh DT, Wang Y, Willingham SB, Ye Z, et al. 2007. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc. Natl. Acad. Sci. USA 104:8041-46. (Pubitemid 47185872)
22. Willingham SB, Bergstralh DT, O'Connor W, Morrison AC, Taxman DJ, et al. 2007. Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC. Cell Host Microbe 2:147-59. (Pubitemid 47355205)
23. Saito M, Nishikomori R, Kambe N, Fujisawa A, Tanizaki H, et al. 2008. Disease-associated CIAS1mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients. Blood 111:2132-41. (Pubitemid 351451525)
24. Meng G, Zhang F, Fuss I, Kitani A, Strober W. 2009.Amutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30:860-74.
25. Brydges SD, Mueller JL, McGeough MD, Pena CA, Misaghi A, et al. 2009. Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity. Immunity 30:875-87.
26. Rock KL, Latz E, Ontiveros F, Kono H. 2010. The sterile inflammatory response. Annu. Rev. Immunol. 28:321-42.
27. Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, et al. 2009. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. USA 106:20388-93.
28. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, et al. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228-32. (Pubitemid 43372102)
29. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Melchiorri L, et al. 1997. Extracellular ATP triggers IL-1βrelease by activating the purinergic P2Z receptor of human macrophages. J. Immunol. 159:1451-58. (Pubitemid 127484125)
30. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237-41. (Pubitemid 43372104)
31. Martinon F. 2010. Update on biology: uric acid and the activation of immune and inflammatory cells. Curr. Rheumatol. Rep. 12:135-41.
32. 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.
33. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, et al. 2008. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat. Immunol. 9:857-65.
34. Duewell P, Kono H, RaynerKJ, Sirois CM, Vladimer G, et al. 2010.NLRP3inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357-61.
35. Yamasaki K, Muto J, Taylor KR, Cogen AL, Audish D, et al. 2009. NLRP3/cryopyrin is necessary for interleukin-1β(IL-1β) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J. Biol. Chem. 284:12762-71.
36. Rock KL, Kono H. 2008. The inflammatory response to cell death. Annu. Rev. Pathol. 3:99-126. (Pubitemid 351488277)
37. Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, et al. 2010. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am. J. Respir. Crit. Care Med. 182:774-83.
38. Muller T, Paula Vieira R, Grimm M, Durk T, Cicko S, et al. 2010. A potential role for P2X7R in allergic airway inflammation in mice and humans. Am. J. Respir. Cell Mol. Biol. In press.
39. Nakae S, Komiyama Y, Yokoyama H, Nambu A, Umeda M, et al. 2003. IL-1 is required for allergenspecific Th2 cell activation and the development of airway hypersensitivity response. Int. Immunol. 15:483-90. (Pubitemid 36432401)
40. Gasse P, Riteau N, Charron S, Girre S, Fick L, et al. 2009. Uric acid is a danger signal activatingNALP3 inflammasome in lung injury inflammation and fibrosis. Am. J. Respir. Crit. CareMed. 179:903-13.
41. Idzko M, Hammad H, van Nimwegen M, Kool M, Willart MA, et al. 2007. Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat. Med. 13:913-19. (Pubitemid 47222044)
42. Dostert C, Petrilli V, Van Bruggen R, Steele C, MossmanBT, Tschopp J. 2008. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674-77. (Pubitemid 351928351)
43. Cassel SL, Eisenbarth SC, Iyer SS, Sadler JJ, Colegio OR, et al. 2008. The Nalp3 inflammasome is essential for the development of silicosis. Proc. Natl. Acad. Sci. USA 105:9035-40.
44. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, et al. 2008. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9:847-56.
45. Caicedo MS, Desai R, McAllister K, Reddy A, Jacobs JJ, Hallab NJ. 2009. Soluble and particulateCo-Cr- Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J. Orthop. Res. 27:847-54.
46. Maitra R, Clement CC, Scharf B, CrisiGM, Chitta S, et al. 2009. Endosomal damage andTLR2mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol. Immunol. 47:175-84.
47. Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. 2008. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122-26. (Pubitemid 351871731)
48. Li H, Willingham SB, Ting JP, Re F. 2008. Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3. J. Immunol. 181:17-21.
49. Franchi L, Nunez G. 2008. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1βsecretion but dispensable for adjuvant activity. Eur. J. Immunol. 38:2085-89.
50. Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, et al. 2008. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J. Immunol. 181:3755-59.
51. McKee AS, Munks MW, MacLeod MK, Fleenor CJ, Van Rooijen N, et al. 2009. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J. Immunol. 183:4403-14.
52. Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. 2007. The inflammasome mediates UVB-induced activation and secretion of interleukin-1βby keratinocytes. Curr. Biol. 17:1140-45. (Pubitemid 46990888)
53. Watanabe H, Gaide O, Petrilli V, Martinon F, Contassot E, et al. 2007. Activation of the IL-1β- processing inflammasome is involved in contact hypersensitivity. J. Investig. Dermatol. 127:1956-63. (Pubitemid 47075373)
54. Broz P, Newton K, Lamkanfi M, Mariathasan S, Dixit VM, Monack DM. 2010. Redundant roles for inflammasome receptorsNLRP3 andNLRC4 in host defense against Salmonella. J. Exp.Med. 207:1745-55.
55. Warren SE, Mao DP, Rodriguez AE, Miao EA, Aderem A. 2008. Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J. Immunol. 180:7558-64.
56. Craven RR, Gao X, Allen IC, Gris D, Bubeck Wardenburg J, et al. 2009. Staphylococcus aureus α- hemolysin activates theNLRP3-inflammasome in human and mousemonocytic cells. PLoSONE4:e7446.
57. Munoz-Planillo R, Franchi L, Miller LS, Nunez G. 2009. A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J. Immunol. 183:3942-48.
58. Meixenberger K, Pache F, Eitel J, Schmeck B, Hippenstiel S, et al. 2010. Listeria monocytogenes-infected human peripheral blood mononuclear cells produce IL-1β, depending on listeriolysin O and NLRP3. J. Immunol. 184:922-30.
59. Ng J, Hirota SA, Gross O, Li Y, Ulke-Lemee A, et al. 2010. Clostridium difficile toxin-induced inflammation and intestinal injury are mediated by the inflammasome. Gastroenterology 139:542-52.
60. Chu J, Thomas LM, Watkins SC, Franchi L, Nunez G, Salter RD. 2009. Cholesterol-dependent cytolysins induce rapid release of mature IL-1βfrom murine macrophages in a NLRP3 inflammasome and cathepsin B-dependent manner. J. Leukoc. Biol. 86:1227-38.
61. Gurcel L, Abrami L, Girardin S, Tschopp J, Van Der Goot FG. 2006. Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival. Cell 126:1135-45. (Pubitemid 44380297)
62. Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. 2009. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med. 206:79-87.
63. Thomas PG, Dash P, Aldridge JR Jr, Ellebedy AH, Reynolds C, et al. 2009. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 30:566-75.
64. Ichinohe T, Pang IK, Iwasaki A. 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat. Immunol. 11:404-10.
65. Muruve DA, Petrilli V, Zaiss AK, White LR, Clark SA, et al. 2008. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452:103-7. (Pubitemid 351355095)
66. Delaloye J, Roger T, Steiner-Tardivel QG, Le Roy D, Knaup Reymond M, et al. 2009. Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome. PLoS Pathog. 5:e1000480.
67. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514-18.
68. Vonk AG, Netea MG, van Krieken JH, Iwakura Y, Van Der Meer JW, Kullberg BJ. 2006. Endogenous interleukin (IL)-1αand IL-1βare crucial for host defense against disseminated candidiasis. J. Infect. Dis. 193:1419-26. (Pubitemid 43673390)
69. Lamkanfi M, Malireddi RK, Kanneganti TD. 2009. Fungal zymosan and mannan activate the cryopyrin inflammasome. J. Biol. Chem. 284:20574-81.
70. Said-Sadier N, Padilla E, Langsley G, Ojcius DM. 2010. Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS ONE 5:e10008.
71. Gross O, Poeck H, Bscheider M, Dostert C, Hannesschlager N, et al. 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459:433-36.
72. Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, 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.
73. Joly S, Ma N, Sadler JJ, Soll DR, Cassel SL, Sutterwala FS. 2009. Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol. 183:3578-81.
74. Shio MT, Eisenbarth SC, Savaria M, Vinet AF, Bellemare MJ, et al. 2009. Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog. 5:e1000559.
75. Coban C, Igari Y, Yagi M, Reimer T, Koyama S, et al. 2010. Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9. Cell Host Microbe 7:50-61.
76. Reimer T, ShawMH, Franchi L, Coban C, Ishii KJ, et al. 2010. Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome. Eur. J. Immunol. 40:764-69.
77. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, et al. 2004. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213-18. (Pubitemid 38902430)
78. Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M, et al. 2007. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 3:e111.
79. Cooney R, Baker J, Brain O, Danis B, Pichulik T, et al. 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16:90-97.
80. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, et al. 2010. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11:55-62.
81. Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA. 2007. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 204:3235-45.
82. Miao EA, Ernst RK, Dors M, Mao DP, Aderem A. 2008. Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proc. Natl. Acad. Sci. USA 105:2562-67. (Pubitemid 351520553)
83. Diez E, Lee SH, Gauthier S, Yaraghi Z, Tremblay M, et al. 2003. Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila. Nat. Genet. 33:55-60. (Pubitemid 36068682)
84. Vinzing M, Eitel J, Lippmann J, Hocke AC, Zahlten J, et al. 2008. NAIP and Ipaf control Legionella pneumophila replication in human cells. J. Immunol. 180:6808-15.
85. Ren T, Zamboni DS, Roy CR, Dietrich WF, Vance RE. 2006. Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog. 2:e18.
86. Lightfield KL, Persson J, Brubaker SW, Witte CE, von Moltke J, et al. 2008. Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat. Immunol. 9:1171-78.
87. ZamboniDS, KobayashiKS, Kohlsdorf T, Ogura Y, Long EM, et al. 2006. The Birc1e cytosolic patternrecognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat. Immunol. 7:318-25.
88. Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW, et al. 2006. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1βvia Ipaf. Nat. Immunol. 7:569-75. (Pubitemid 43797337)
89. Franchi L, Amer A, Body-Malapel M, KannegantiTD, Ozoren N, et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1βin salmonella-infected macrophages. Nat. Immunol. 7:576-82. (Pubitemid 43797338)
90. Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, et al. 2010. Innate immune detection of the type III secretion apparatus through theNLRC4 inflammasome. Proc. Natl. Acad. Sci. USA 107:3076-80.
91. 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. 14:1583-89. (Pubitemid 47278844)
92. Arlehamn CS, Petrilli V, Gross O, Tschopp J, Evans TJ. The role of potassium in inflammasome activation by bacteria. J. Biol. Chem. 285:10508-18.
93. Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, et al. 2007. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J. Histochem. Cytochem. 55:443-52. (Pubitemid 46668626)
94. Hlaing T, Guo RF, Dilley KA, Loussia JM, Morrish TA, et al. 2001. Molecular cloning and characterization of DEFCAP-L and -S, two isoforms of a novel member of the mammalian Ced-4 family of apoptosis proteins. J. Biol. Chem. 276:9230-38.
95. Boyden ED, Dietrich WF. 2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat. Genet. 38:240-44. (Pubitemid 43177241)
96. Nour AM, Yeung YG, Santambrogio L, Boyden ED, Stanley ER, Brojatsch J. 2009. Anthrax lethal toxin triggers the formation of a membrane-associated inflammasome complex in murine macrophages. Infect. Immun. 77:1262-71.
97. Hanna PC, Acosta D, Collier RJ. 1993. On the role of macrophages in anthrax. Proc. Natl. Acad. Sci. USA 90:10198-201. (Pubitemid 23328279)
98. Terra JK, Cote CK, France B, Jenkins AL, Bozue JA, et al. 2010. Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J. Immunol. 184:17-20.
99. Liao KC, Mogridge J. 2009. Expression of Nlrp1b inflammasome components in human fibroblasts confers susceptibility to anthrax lethal toxin. Infect. Immun. 77:4455-62.
100. DeYoung KL, Ray ME, Su YA, Anzick SL, Johnstone RW, et al. 1997. Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. Oncogene 15:453-57. (Pubitemid 27370995)
101. Hornung V, Latz E. 2010. Intracellular DNA recognition. Nat. Rev. Immunol. 10:123-30.
102. Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, et al. 2010. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11:385-93.
103. Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, et al. 2010. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11:395-402.
104. Sauer JD, Witte CE, Zemansky J, Hanson B, Lauer P, Portnoy DA. 2010. Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe 7:412-19.
105. Franchi L, Eigenbrod T, NunezG. 2009. Cutting edge: TNF-αmediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J. Immunol. 183:792-96.
106. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, 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.
107. Meissner F, Molawi K, Zychlinsky A. 2008. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat. Immunol. 9:866-72.
108. Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. 2010. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood 116:1570-73.
109. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. 2010. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 11:136-40.
110. Masters SL, Dunne A, Subramaanian SL, Hull RL, Tannahill GM, et al. 2010. Activation of theNLRP3 inflammasome by islet amyloid polypeptide provides amechanism for enhanced IL-1βin type 2 diabetes. Nat. Immunol. 11:897-904.
111. Bryan NB, Dorfleutner A, Kramer SJ, Yun C, Rojanasakul Y, Stehlik C. 2010. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes. J. Inflamm. 7:23.
112. Rosenstiel P, Huse K, Till A, Hampe J, Hellmig S, et al. 2006. A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor ofNOD2/receptor- interacting protein kinase 2-induced signaling pathways. Proc. Natl. Acad. Sci. USA 103:3280-85. (Pubitemid 43346461)
113. Stehlik C, Dorfleutner A. 2007. COPs and POPs: modulators of inflammasome activity. J. Immunol. 179:7993-98.
114. Chae JJ, Komarow HD, Cheng J, Wood G, Raben N, et al. 2003. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol. Cell 11:591-604. (Pubitemid 36385116)
115. Chae JJ, Wood G, Masters SL, Richard K, Park G, et al. 2006. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1βproduction. Proc. Natl. Acad. Sci. USA 103:9982-87. (Pubitemid 43993609)
116. Yu JW, Wu J, Zhang Z, Datta P, Ibrahimi I, et al. 2006. Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization. Cell Death Differ. 13:236-49. (Pubitemid 43102207)
117. Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, et al. 2007. Pyrin activates theASCpyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol. Cell 28:214-27. (Pubitemid 47600003)
118. Young JL, Sukhova GK, Foster D, Kisiel W, Libby P, Schonbeck U. 2000. The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1β-converting enzyme (caspase-1) activity in human vascular smooth muscle cells. J. Exp. Med. 191:1535-44. (Pubitemid 30257350)
119. Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, et al. 2007. Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 129:45-56. (Pubitemid 46507581)
120. Guarda G, Dostert C, Staehli F, Cabalzar K, Castillo R, et al. 2009. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature 460:269-73.
121. Taxman DJ, Huang MT, Ting JP. 2010. Inflammasome inhibition as a pathogenic stealth mechanism. Cell Host Microbe 8:7-11.
122. Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR, et al. 1992. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1βconverting enzyme. Cell 69:597-604.
123. Dobo J, Swanson R, Salvesen GS, Olson ST, Gettins PG. 2006. Cytokine response modifier A inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramer. J. Biol. Chem. 281:38781-90. (Pubitemid 46042005)
124. Kettle S, Alcami A, Khanna A, Ehret R, Jassoy C, Smith GL. 1997. Vaccinia virus serpin B13R (SPI- 2) inhibits interleukin-1β-converting enzyme and protects virus-infected cells from TNF- and Fasmediated apoptosis, but does not prevent IL-1β-induced fever. J. Gen. Virol. 78(Pt. 3):677-85. (Pubitemid 27116792)
125. Johnston JB, Barrett JW, Nazarian SH, Goodwin M, Ricciuto D, et al. 2005. A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 23:587-98. (Pubitemid 41779481)
126. Rahman MM, MohamedMR, Kim M, Smallwood S, McFadden G. 2009. Co-regulation of NF-κB and inflammasome-mediated inflammatory responses by myxoma virus pyrin domain-containing protein M013. PLoS Pathog. 5:e1000635.
127. Dorfleutner A, Bryan NB, Talbott SJ, Funya KN, Rellick SL, et al. 2007. Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation. Infect. Immun. 75:1484-92. (Pubitemid 46385842)
128. Stasakova J, Ferko B, Kittel C, Sereinig S, Romanova J, et al. 2005. Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1βand 18. J. Gen. Virol. 86:185-95. (Pubitemid 40081165)
129. Bump NJ, Hackett M, Hugunin M, Seshagiri S, Brady K, et al. 1995. Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269:1885-88.
130. Brodsky IE, Palm NW, Sadanand S, Ryndak MB, Sutterwala FS, et al. 2010. A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. Cell Host Microbe 7:376-87.
131. Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R. 2004. Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1β. J. Biol. Chem. 279:25134-42. (Pubitemid 38756762)
132. Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, et al. 2006. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24:317-27.
133. Mayer-BarberKD, Barber DL, Shenderov K, White SD, Wilson MS, et al. 2010. Caspase-1 independent IL-1βproduction is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J. Immunol. 184:3326-30.
134. Mishra BB, Moura-Alves P, Sonawane A, Hacohen N, Griffiths G, et al. 2010. Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol. 12:1046-63.
135. Master SS, Rampini SK, Davis AS, Keller C, Ehlers S, et al. 2008. Mycobacterium tuberculosis prevents inflammasome activation. Cell Host Microbe 3:224-32. (Pubitemid 351494718)
136. HuangMT, Mortensen BL, Taxman DJ, Craven RR, Taft-Benz S, et al. 2010. Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. J. Immunol. 185:5476-85.
137. UllandTK, Buchan BW, KettererMR, Fernandes-Alnemri T, Meyerholz DK, et al. 2010. Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence. J. Immunol. 185:2670-74.
138. Littmann M, Albiger B, Frentzen A, Normark S, Henriques-Normark B, Plant L. 2009. Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression.EMBOMol.Med. 1:211-22.
139. World Health Organization. 2002. TheWorld Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva:WHO.
140. Zimmet P, Alberti KG, Shaw J. 2001. Global and societal implications of the diabetes epidemic. Nature 414:782-87. (Pubitemid 34000780)
141. Hotamisligil GS. 2006. Inflammation and metabolic disorders. Nature 444:860-67. (Pubitemid 46024993)
142. Feve B, Bastard JP. 2009. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat. Rev. Endocrinol. 5:305-11.
143. Hansson GK. 2005. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352:1685-95.
144. Lagathu C, Yvan-Charvet L, Bastard JP, Maachi M, Quignard-Boulange A, et al. 2006. Long-term treatment with interleukin-1βinduces insulin resistance in murine and human adipocytes. Diabetologia 49:2162-73. (Pubitemid 44168485)
145. Mandrup-Poulsen T, Pickersgill L, Donath MY. 2010. Blockade of interleukin 1 in type 1 diabetes mellitus. Nat. Rev. Endocrinol. 6:158-66.
146. Kirii H, Niwa T, Yamada Y, Wada H, Saito K, et al. 2003. Lack of interleukin-1βdecreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler. Thromb. Vasc. Biol. 23:656-60. (Pubitemid 36438080)
147. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, et al. 2007. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356:1517-26. (Pubitemid 46588416)
148. Lamkanfi M, Mueller JL, VitariAC, Misaghi S, Fedorova A, et al. 2009. Glyburide inhibits theCryopyrin/ Nalp3 inflammasome. J. Cell Biol. 187:61-70.
149. Smith PE, Brender JR, Ramamoorthy A. 2009. Induction of negative curvature as a mechanism of cell toxicity by amyloidogenic peptides: the case of islet amyloid polypeptide. J. Am. Chem. Soc. 131:4470-78.
150. Galkina E, Ley K. 2009. Immune and inflammatory mechanisms of atherosclerosis. Annu. Rev. Immunol. 27:165-97.
151. Clevers H. 2004. At the crossroads of inflammation and cancer. Cell 118:671-74. (Pubitemid 39221727)
152. Karin M, Greten FR. 2005. NF-κB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5:749-59. (Pubitemid 41400849)
153. Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, et al. 2010. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J. Exp.Med. 207:1045-56.
154. Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD. 2010. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32:379-91.
155. Dupaul-Chicoine J, Yeretssian G, Doiron K, Bergstrom KS, McIntire CR, et al. 2010. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32:367-78.
156. Dinarello CA. 2009. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27:519-50.
157. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, et al. 2010. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J. Exp. Med. 207:1625-36.
158. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, et al. 2009. Activation of the NLRP3 in- flammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nat. Med. 15:1170-78.
159. Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, et al. 2009. Acetaminopheninduced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J. Clin. Investig. 119:305-14.
160. Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, et al. 2009. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30:576-87.
161. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. 2009. Interleukin-1 and IL-23 induce innate IL-17 production from γT cells, amplifying Th17 responses and autoimmunity. Immunity 31:331-41.
162. Wilson NJ, Boniface K, Chan JR, McKenzie BS, BlumenscheinWM, et al. 2007. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat. Immunol. 8:950-57. (Pubitemid 47300009)
163. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. 2007. Interleukins 1βand 6 but not transforming growth factor-βare essential for the differentiation of interleukin 17-producing human T helper cells. Nat. Immunol. 8:942-49. (Pubitemid 47300008)
164. Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, et al. 1997. IGIF does not drive Th1 development but synergizeswith IL-12 for interferon- γproduction and activates IRAK andNFκB. Immunity 7:571-81. (Pubitemid 27508708)
165. Gris D, Ye Z, Iocca HA, Wen H, Craven RR, et al. 2010. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J. Immunol. 185:974-81.
166. Shaw PJ, Lukens JR, Burns S, Chi H, McGargill MA, Kanneganti TD. 2010. Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. J. Immunol. 184:4610-4.
167. Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C, 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.
168. Kolly L, Karababa M, Joosten LA, Narayan S, Salvi R, et al. 2009. Inflammatory role of ASC in antigeninduced arthritis is independent of caspase-1, NALP-3, and IPAF. J. Immunol. 183:4003-12.
169. Ting JP, Duncan JA, Lei Y. 2010. How the noninflammasome NLRs function in the innate immune system. Science 327:286-90.
170. Lich JD, WilliamsKL, MooreCB, Arthur JC, Davis BK, et al. 2007. Monarch-1 suppresses non-canonical NF-κB activation and p52-dependent chemokine expression in monocytes. J. Immunol. 178:1256-60. (Pubitemid 46154594)
171. Cui J, Zhu L, Xia X, Wang HY, Legras X, et al. 2010. NLRC5 negatively regulates the NF-κB and type I interferon signaling pathways. Cell 141:483-96.
172. Kuenzel S, Till A, Winkler M, Hasler R, Lipinski S, et al. 2010. The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses. J. Immunol. 184:1990-2000.
173. Neerincx A, Lautz K, Menning M, Kremmer E, Zigrino P, et al. 2010. A role for the human nucleotidebinding domain, leucine-rich repeat-containing family member NLRC5 in antiviral responses. J. Biol. Chem. 285:26223-32.
174. Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, et al. 2008. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451:573-77. (Pubitemid 351186265)
175. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, et al. 2009. Activation of innate immune antiviral responses by Nod2. Nat. Immunol. 10:1073-80