The inflammasomes: Molecular effectors of host resistance against bacterial, viral, parasitic, and fungal infections

Frontiers in Microbiology

Volumn 2, Issue FEB, 2011, Pages

  Skeldon, Alexander ^a   Saleh, Maya ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Caspases; Infection; Inflammasome; Inflammation; Innate immunity; Nod like receptors

Indexed keywords

EID: 80855164150     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2011.00015     Document Type: Article

References (160)

1. Akhter, A., Gavrilin, M. A., Frantz, L., Washington, S., Ditty, C., Limoli, D., Day, C., Sarkar, A., Newland, C., Butchar, J., Marsh, C. B., Wewers, M. D., Tridandapani, S., Kanneganti, T. D., and Amer, A. O. (2009). Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection. PLoS Pathog. 5, e1000361. doi:10.1371/journal.ppat.1000361
2. Alcami, A., and Smith, G. L. (1992). A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71, 153-16
3. Allen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-Tekippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., and Ting, J. P. (2009). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556-56
4. Allen, I. C., Tekippe, E. M., Woodford, R. M. T., Uronis, J. M., Holl, E. K., Rogers, A. B., Herfarth, H. H., Jobin, C., and Ting, J. P. Y. (2010). The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J. Exp. Med. 207, 1045-105
5. Amer, A., Franchi, L., Kanneganti, T. D., Body-Malapel, M., Ozoren, N., Brady, G., Meshinchi, S., Jagirdar, R., Gewirtz, A., Akira, S., and Nunez, G. (2006). Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J. Biol. Chem. 281, 35217-3522
6. Arlehamn, C. S., Petrilli, V., Gross, O., Tschopp, J., and Evans, T. J. (2010). The role of potassium in inflammasome activation by bacteria. J. Biol. Chem. 285, 10508-1051
7. Belkhadir, Y., Subramaniam, R., and Dangl, J. L. (2004). Plant disease resistance protein signaling: NBS-LRR proteins and their partners. Curr. Opin. Plant Biol. 7, 391-39
8. Bianchi, M. E. (2007). DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81, 1-5.
9. Boyden, E. D., and Dietrich, W. F. (2006). Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat. Genet. 38, 240-24
10. Brodsky, I. E., Palm, N. W., Sadanand, S., Ryndak, M. B., Sutterwala, F. S., Flavell, R. A., Bliska, J. B., and Medzhitov, R. (2010). A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. Cell Host Microbe 7, 376-38
11. Broz, P., Newton, K., Lamkanfi, M., Mariathasan, S., Dixit, V. M., and Monack, D. M. (2010). Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J. Exp. Med. 207, 1745-175
12. Bruey, J. M., Bruey-Sedano, N., Luciano, F., Zhai, D., Balpai, R., Xu, C., et al. (2007). Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 129, 45-5
13. Carlsson, F., Kim, J., Dumitru, C., Barck, K. H., Carano, R. A., Sun, M., Diehl, L., and Brown, E. J. (2010). Hostdetrimental role of Esx-1-mediated inflammasome activation in mycobacterial infection. PLoS Pathog. 6, e1000895. doi:10.1371/journal. ppat.1000895
14. Case, C. L., Shin, S., and Roy, C. R. (2009). Asc and Ipaf Inflammasomes direct distinct pathways for caspase-1 activation in response to Legionella pneumophila. Infect. Immun. 77, 1981-199
15. Cassel, S. L., Eisenbarth, S. C., Iyer, S. S., Sadler, J. J., Colegio, O. R., Tephly, L. A., Carter, A. B., Rothman, P. B., Flavell, R. A., and Sutterwala, F. S. (2008). The Nalp3 inflammasome is essential for the development of silicosis. Proc. Natl. Acad. Sci. U.S.A. 105, 9035-904
16. Cervantes, J., Nagata, T., Uchijima, M., Shibata, K., and Koide, Y. (2008). Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages. Cell. Microbiol. 10, 41-5
17. Chaix, J., Tessmer, M. S., Hoebe, K., Fuseri, N., Ryffel, B., Dalod, M., Alexopoulou, L., Beutler, B., Brossay, L., Vivier, E., and Walzer, T. (2008). Cutting edge: priming of NK cells by IL-18. J. Immunol. 181, 1627-163
18. Chamaillard, M., Hashimoto, M., Horie, Y., Masumoto, J., Qiu, S., Saab, L., Ogura, Y., Kawasaki, A., Fukase, K., Kusumoto, S., Valvano, M. A., Foster, S. J., Mak, T. W., Nunez, G., and Inohara, N. (2003). An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat. Immunol. 4, 702-70
19. Coers, J., Vance, R. E., Fontana, M. F., and Dietrich, W. F. (2007). Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. Cell. Microbiol. 9, 2344-235
20. Collier, R. J., and Young, J. A. (2003). Anthrax toxin. Annu. Rev. Cell Dev. Biol. 19, 45-7
21. Craven, R. R., Gao, X., Allen, I. C., Gris, D., Bubeck Wardenburg, J., McElvania-Tekippe, E., Ting, J. P., and Duncan, J. A. (2009). Staphylococcus aureus α-hemolysin activates the NLRP3inflammasome in human and mouse monocytic cells. PLoS ONE 4, e7446. doi:10.1371/journal.pone.0007446
22. Diez, E., Lee, S. H., Gauthier, S., Yaraghi, Z., Tremblay, M., Vidal, S., and Gros, P. (2003). Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila. Nat. Genet. 33, 55-6
23. Dorfleutner, A., Bryan, N. B., Talbott, S. J., Funya, K. N., Rellick, S. L., Reed, J. C., Shi, X., Rojanasakul, Y., Flynn, D. C., and Stehlik, C. (2007). Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation. Infect. Immun. 75, 1484-149
24. Dostert, C., Guarda, G., Romero, J. F., Menu, P., Gross, O., Tardivel, A., Suva, M. L., Stehle, J. C., Kopf, M., Stamenkovic, I., Corradin, G., and Tschopp, J. (2009). Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS ONE 4, e6510. doi:10.1371/journal.pone.0006510
25. Dostert, C., Petrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., and Tschopp, J. (2008). Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674-67
26. Duesbery, N. S., Webb, C. P., Leppla, S. H., Gordon, V. M., Klimpel, K. R., Copeland, T. D., Ahn, N. G., Oskarsson, M. K., Fukasawa, K., Paull, K. D., and Vande Woude, G. F. (1998). Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280, 734-73
27. Dupaul-Chicoine, J., Yeretssian, G., Doiron, K., Bergstrom, K. S., Mcintire, C. R., Leblanc, P. M., Meunier, C., Turbide, C., Gros, P., Beauchemin, N., Vallance, B. A., and Saleh, M. (2010). Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32, 367-37
28. Faustin, B., Chen, Y., Zhai, D. Y., Le Negrate, G., Lartigue, L., Satterthwait, A., and Reed, J. C. (2009). Mechanism of Bcl-2 and Bcl-X-L inhibition of NLRP1 inflammasome: loop domain-dependent suppression of ATP binding and oligomerization. Proc. Natl. Acad. Sci. U.S.A. 106, 3935-394
29. Faustin, B., Lartigue, L., Bruey, J. M., Luciano, F., Sergienko, E., BaillyMaitre, B., Volkmann, N., Hanein, D., Rouiller, I., and Reed, J. C. (2007). Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol. Cell 25, 713-72
30. Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J., and Alnemri, E. S. (2009). AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509-51
31. Fernandes-Alnemri, T., Yu, J. W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., Mccormick, M., Huang, L., Mcdermott, E., Eisenlohr, L., Landel, C. P., and Alnemri, E. S. (2010). The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11, 385-39
32. Fink, S. L., Bergsbaken, T., and Cookson, B. T. (2008). Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1dependent pyroptosis via distinct mechanisms. Proc. Natl. Acad. Sci. U.S.A. 105, 4312-431
33. Fink, S. L., and Cookson, B. T. (2005). Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907-191
34. Flynn, J. L., and Chan, J. (2001). Immunology of tuberculosis. Annu. Rev. Immunol. 19, 93-12
35. Fortier, A., de Chastellier, C., Balor, S., and Gros, P. (2007). Birc1e/Naip5 rapidly antagonizes modulation of phagosome maturation by Legionella pneumophila. Cell. Microbiol. 9, 910-92
36. Fortier, A., Doiron, K., Saleh, M., Grinstein, S., and Gros, P. (2009). Restriction of Legionella pneumophila replication in macrophages requires concerted action of the transcriptional regulators Irf1 and Irf8 and nod-like receptors Naip5 and Nlrc4. Infect. Immun. 77, 4794-480
37. Franchi, L., Amer, A., Body-Malapel, M., Kanneganti, T. D., Ozoren, N., Jagirdar, R., Inohara, N., Vandenabeele, P., Bertin, J., Coyle, A., Grant, E. P., and Nunez, G. (2006). Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in Salmonella-infected macrophages. Nat. Immunol. 7, 576-58
38. Franchi, L., Kanneganti, T. D., Dubyak, G. R., and Nunez, G. (2007). Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. J. Biol. Chem. 282, 18810-1881
39. Fremond, C. M., Togbe, D., Doz, E., Rose, S., Vasseur, V., Maillet, I., Jacobs, M., Ryffel, B., and Quesniaux, V. F. (2007). IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J. Immunol. 179, 1178-118
40. Gabay, C., Lamacchia, C., and Palmer, G. (2010). IL-1 pathways in inflammation and human diseases. Nat. Rev. Rheumatol. 6, 232-24
41. Gavrilin, M. A., Bouakl, I. J., Knatz, N. L., Duncan, M. D., Hall, M. W., Gunn, J. S., and Wewers, M. D. (2006). Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc. Natl. Acad. Sci. U.S.A. 103, 141-14
42. 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., and Allen, H. (1997). Caspase-1 processes IFN-gammainducing factor and regulates LPSinduced IFN-gamma production. Nature 386, 619-62
43. Girardin, S. E., Boneca, I. G., Carneiro, L.a.M., Antignac, A., Jehanno, M., Viala, J., Tedin, K., Taha, M. K., Labigne, A., Zahringer, U., Coyle, A. J., Bertin, J., Sansonetti, P. J., and Philpott, D. J. (2003). Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300, 1584-158
44. Griffith, J. W., Sun, T., McIntosh, M. T., and Bucala, R. (2009). Pure hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid. J. Immunol. 183, 5208-522
45. Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschlager, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V., Mocsai, A., Tschopp, J., and Ruland, J. (2009). Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459, 433-43
46. Gu, Y., Kuida, K., Tsutsui, H., Ku, G., Hsiao, K., Fleming, M. A., Hayashi, N., Higashino, K., Okamura, H., Nakanishi, K., Kurimoto, M., Tanimoto, T., Flavell, R. A., Sato, V., Harding, M. W., Livingston, D. J., and Su, M. S. S. (1997). Activation of interferon-gamma inducing factor mediated by interleukin-1 beta converting enzyme. Science 275, 206-20
47. Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., and Golenbock, D. T. (2008). The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat. Immunol. 9, 857-865.
48. Hanscheid, T., Egan, T. J., and Grobusch, M. P. (2007). Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator. Lancet Infect. Dis. 7, 675-68
49. Hara, H., Tsuchiya, K., Nomura, T., Kawamura, I., Shoma, S., and Mitsuyama, M. (2008). Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm. J. Immunol. 180, 7859-786
50. Haraga, A., Ohlson, M. B., and Miller, S. I. (2008). Salmonellae interplay with host cells. Nat. Rev. Microbiol. 6, 53-6
51. Hardt, W. D., Chen, L. M., Schuebel, K. E., Bustelo, X. R., and Galan, J. E. (1998). S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93, 815-82
52. Hennet, T., Ziltener, H. J., Frei, K., and Peterhans, E. (1992). A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J. Immunol. 149, 932-93
53. Henry, T., Brotcke, A., Weiss, D. S., Thompson, L. J., and Monack, D. M. (2007). Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J. Exp. Med. 204, 987-99
54. Hersh, D., Monack, D. M., Smith, M. R., Ghori, N., Falkow, S., and Zychlinsky, A. (1999). The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc. Natl. Acad. Sci. U.S.A. 96, 2396-240
55. Hise, A. G., Tomalka, J., Ganesan, S., Patel, K., Hall, B. A., Brown, G. D., and Fitzgerald, K. A. (2009). An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 5, 487-49
56. Hoffmann, C., Galle, M., Dilling, S., Kappeli, R., Muller, A. J., Songhet, P., Beyaert, R., and Hardt, W. D. (2010). In macrophages, caspase-1 activation by SopE and the type III secretion system-1 of S. typhimurium can proceed in the absence of flagellin. PLoS ONE 5, e12477. doi:10.1371/journal. pone.0012477
57. Hornung, V., Ablasser, A., CharrelDennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., and Fitzgerald, K. A. (2009). AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514-51
58. Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., and Latz, E. (2008). Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847-85
59. Hsu, L. C., Ali, S. R., Mcgillivray, S., Tseng, P. H., Mariathasan, S., Humke, E. W., Eckmann, L., Powell, J. J., Nizet, V., Dixit, V. M., and Karin, M. (2008). A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc. Natl. Acad. Sci. U.S.A. 105, 7803-780
60. Hyodo, Y., Matsui, K., Hayashi, N., Tsutsui, H., Kashiwamura, S., Yamauchi, H., Hiroishi, K., Takeda, K., Tagawa, Y., Iwakura, Y., Kayagaki, N., Kurimoto, M., Okamura, H., Hada, T., Yagita, H., Akira, S., Nakanishi, K., and Higashino, K. (1999). IL-18 up-regulates perforinmediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J. Immunol. 162, 1662-166
61. Ichinohe, T., Lee, H. K., Ogura, Y., Flavell, R., and Iwasaki, A. (2009). Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med. 206, 79-8
62. Ichinohe, T., Pang, I. K., and Iwasaki, A. (2010). Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat. Immunol. 11, 404-41
63. Inohara, N., Ogura, Y., Fontalba, A., Gutierrez, O., Pons, F., Crespo, J., Fukase, K., Inamura, S., Kusumoto, S., Hashimoto, M., Foster, S. J., Moran, A. P., Fernandez-Luna, J. L., and Nunez, G. (2003). Host recognition of bacterial muramyl dipeptide mediated through NOD2. J. Biol. Chem. 278, 5509-551
64. Isberg, R. R., O'Connor, T. J., and Heidtman, M. (2009). The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat. Rev. Microbiol. 7, 13-2
65. Johnston, J. B., Barrett, J. W., Nazarian, S. H., Goodwin, M., Ricciuto, D., Wang, G., and McFadden, G. (2005). A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 23, 587-59
66. Joly, S., Ma, N., Sadler, J. J., Soll, D. R., Cassel, S. L., and Sutterwala, F. S. (2009). Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol. 183, 3578-358
67. Jones, J. W., Kayagaki, N., Broz, P., Henry, T., Newton, K., O'Rourke, K., Chan, S., Dong, J., Qu, Y., Roose-Girma, M., Dixit, V. M., and Monack, D. M. (2010). Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc. Natl. Acad. Sci. U.S.A. 107, 9771-977
68. Juffermans, N. P., Florquin, S., Camoglio, L., Verbon, A., Kolk, A. H., Speelman, P., Van Deventer, S. J., and Van Der Poll, T. (2000). Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis. J. Infect. Dis. 182, 902-90
69. Kanneganti, T. D., Body-Malapel, M., Amer, A., Park, J. H., Whitfield, J., Franchi, L., Taraporewala, Z. F., Miller, D., Patton, J. T., Inohara, N., and Nunez, G. (2006). Critical role for cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 281, 36560-3656
70. Keller, M., Ruegg, A., Werner, S., and Beer, H. D. (2008). Active caspase-1 is a regulator of unconventional protein secretion. Cell 132, 818-83
71. Kim, S., Bauernfeind, F., Ablasser, A., Hartmann, G., Fitzgerald, K. A., Latz, E., and Hornung, V. (2010). Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur. J. Immunol. 40, 1545-155
72. Koo, I. C., Wang, C., Raghavan, S., Morisaki, J. H., Cox, J. S., and Brown, E. J. (2008). ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection. Cell. Microbiol. 10, 1866-187
73. Kumar, H., Kumagai, Y., Tsuchida, T., Koenig, P. A., Satoh, T., Guo, Z., Jang, M. H., Saitoh, T., Akira, S., and Kawai, T. (2009). Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal beta-glucan. J. Immunol. 183, 8061-806
74. Kurenuma, T., Kawamura, I., Hara, H., Uchiyama, R., Daim, S., Dewamitta, S. R., Sakai, S., Tsuchiya, K., Nomura, T., and Mitsuyama, M. (2009). The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. Infect. Immun. 77, 3992-400
75. Labbe, K., Miu, J., Yeretssian, G., Serghides, L., Tam, M., Finney, C. A., Erdman, L. K., Goulet, M. L., Kain, K. C., Stevenson, M. M., and Saleh, M. (2010). Caspase-12 dampens the immune response to malaria independently of the inflammasome by targeting NF-kappaB signaling. J. Immunol. 185, 5495-550
76. Labbe, K., and Saleh, M. (2008). Cell death in the host response to infection. Cell Death Differ. 15, 1339-134
77. Lamkanfi, M., Amer, A., Kanneganti, T. D., Munoz-Planillo, R., Chen, G., Vandenabeele, P., Fortier, A., Gros, P., and Nunez, G. (2007). The Nodlike receptor family member Naip5/ Birc1e restricts Legionella pneumophila growth independently of caspase-1 activation. J. Immunol. 178, 8022-802
78. Lamkanfi, M., Kanneganti, T. D., Van Damme, P., Vanden Berghe, T., Vanoverberghe, I., Vandekerckhove, J., Vandenabeele, P., Gevaert, K., and Nunez, G. (2008). Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes. Mol. Cell Proteomics 7, 2350-236
79. Lara-Tejero, M., Sutterwala, F. S., Ogura, Y., Grant, E. P., Bertin, J., Coyle, A. J., Flavell, R. A., and Galan, J. E. (2006). Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J. Exp. Med. 203, 1407-141
80. Lightfield, K. L., Persson, J., Brubaker, S. W., Witte, C. E., Von Moltke, J., Dunipace, E. A., Henry, T., Sun, Y. H., Cado, D., Dietrich, W. F., Monack, D. M., Tsolis, R. M., and Vance, R. E. (2008). Critical function for Naip5 in inflammasome activation by a conserved carboxyterminal domain of flagellin. Nat. Immunol. 9, 1171-117
81. Lin, X. Y., Choi, M. S. K., and Porter, A. G. (2000). Expression analysis of the human caspase-1 subfamily reveals specific regulation of the CASP5 gene by lipopolysaccharide and interferon-gamma. J. Biol. Chem. 275, 39920-3992
82. Lo, H. J., Kohler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., and Fink, G. R. (1997). Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939-94
83. Mariathasan, S., Newton, K., Monack, D. M., Vucic, D., French, D. M., Lee, W. P., Roose-Girma, M., Erickson, S., and Dixit, V. M. (2004). Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430, 213-21
84. Mariathasan, S., Weiss, D. S., Dixit, V. M., and Monack, D. M. (2005). Innate immunity against Francisella tularensis is dependent on the ASC/ caspase-1 axis. J. Exp. Med. 202, 1043-104
85. Mariathasan, S., Weiss, D. S., Newton, K., Mcbride, J., O'rourke, K., RooseGirma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., and Dixit, V. M. (2006). Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228-23
86. Martinon, F., Burns, K., and Tschopp, J. (2002). The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10, 417-42
87. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A., and Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237-24
88. Master, S. S., Rampini, S. K., Davis, A. S., Keller, C., Ehlers, S., Springer, B., Timmins, G. S., Sander, P., and Deretic, V. (2008). Mycobacterium tuberculosis prevents inflammasome activation. Cell Host Microbe 3, 224-23
89. Mayer-Barber, K. D., Barber, D. L., Shenderov, K., White, S. D., Wilson, M. S., Cheever, A., Kugler, D., Hieny, S., Caspar, P., Nunez, G., Schlueter, D., Flavell, R. A., Sutterwala, F. S., and Sher, A. (2010). Caspase-1 independent IL-1beta production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J. Immunol. 184, 3326-333
90. McElvania-Tekippe, E., Allen, I. C., Hulseberg, P. D., Sullivan, J. T., McCann, J. R., Sandor, M., Braunstein, M., and Ting, J. P. (2010). Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLoS ONE 5, e12320. doi:10.1371/journal.pone.0012320
91. Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature 454, 428-43
92. Meixenberger, K., Pache, F., Eitel, J., Schmeck, B., Hippenstiel, S., Slevogt, H., N'guessan, P., Witzenrath, M., Netea, M. G., Chakraborty, T., Suttorp, N., and Opitz, B. (2010). Listeria monocytogenes-infected human peripheral blood mononuclear cells produce IL-1beta, depending on listeriolysin O and NLRP3. J. Immunol. 184, 922-93
93. Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., and Aderem, A. (2006). Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat. Immunol. 7, 569-57
94. Miao, E. A., Ernst, R. K., Dors, M., Mao, D. P., and Aderem, A. (2008). Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proc. Natl. Acad. Sci. U.S.A. 105, 2562-2567
95. Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., Warren, S. E., Wewers, M. D., and Aderem, A. (2010a). Caspase-1induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat. Immunol. 11, 1136-119
96. Miao, E. A., Mao, D. P., Yudkovsky, N., Bonneau, R., Lorang, C. G., Warren, S. E., Leaf, I. A., and Aderem, A. (2010b). Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc. Natl. Acad. Sci. U.S.A. 107, 3076-308
97. Mishra, B. B., Moura-Alves, P., Sonawane, A., Hacohen, N., Griffiths, G., Moita, L. F., and Anes, E. (2010). Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell. Microbiol. 12, 1046-106
98. Molofsky, A. B., Byrne, B. G., Whitfield, N. N., Madigan, C. A., Fuse, E. T., Tateda, K., and Swanson, M. S. (2006). Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J. Exp. Med. 203, 1093-110
99. Muller, A. J., Hoffmann, C., Galle, M., Van Den Broeke, A., Heikenwalder, M., Falter, L., Misselwitz, B., Kremer, M., Beyaert, R., and Hardt, W. D. (2009). The S. typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. Cell Host Microbe 6, 125-13
100. Muruve, D. A., Petrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., and Tschopp, J. (2008). The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103-10
101. Nakhaei, P., Genin, P., Civas, A., and Hiscott, J. (2009). RIG-I-like receptors: sensing and responding to RNA virus infection. Semin. Immunol. 21, 215-22
102. Netea, M. G., and Marodi, L. (2010). Innate immune mechanisms for recognition and uptake of Candida species. Trends Immunol. 31, 346-35
103. Newman, Z. L., Printz, M. P., Liu, S., Crown, D., Breen, L., MillerRandolph, S., Flodman, P., Leppla, S. H., and Moayeri, M. (2010). Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1. PLoS Pathog. 6, e1000906. doi:10.1371/journal. ppat.1000906
104. O'Neill, L. A., and Bowie, A. G. (2010). Sensing and signaling in antiviral innate immunity. Curr. Biol. 20, R328-R33
105. Ozoren, N., Masumoto, J., Franchi, L., Kanneganti, T. D., Body-Malapel, M., Erturk, I., Jagirdar, R., Zhu, L., Inohara, N., Bertin, J., Coyle, A., Grant, E. P., and 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, 4337-434
106. Pelegrin, P., and Surprenant, A. (2006). Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071-508
107. Petrilli, V., Papin, S., Dostert, C., Mayor, A., Martinon, F., and Tschopp, J. (2007). Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14, 1583-158
108. Pirhonen, J., Sareneva, T., Kurimoto, M., Julkunen, I., and Matikainen, S. (1999). Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1dependent pathway. J. Immunol. 162, 7322-732
109. Poeck, H., Bscheider, M., Gross, O., Finger, K., Roth, S., Rebsamen, M., Hannesschlager, N., Schlee, M., Rothenfusser, S., Barchet, W., Kato, H., Akira, S., Inoue, S., Endres, S., Peschel, C., Hartmann, G., Hornung, V., and Ruland, J. (2010). Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat. Immunol. 11, 63-6
110. Proell, M., Riedl, S. J., Fritz, J. H., Rojas, A. M., and Schwarzenbacher, R. (2008). The Nod-like receptor (NLR) family: a tale of similarities and differences. PLoS ONE 3, e2119. doi:10.1371/ journal.pone.0002119
111. Rathinam, V. A., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., Hornung, V., Vogel, S. N., Szomolanyi-Tsuda, E., and Fitzgerald, K. A. (2010). The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395-40
112. Raupach, B., Peuschel, S. K., Monack, D. M., and Zychlinsky, A. (2006). Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect. Immun. 74, 4922-492
113. Reig, N., Jiang, A., Couture, R., Sutterwala, F. S., Ogura, Y., Flavell, R. A., Mellman, I., and Van Der Goot, F. G. (2008). Maturation modulates caspase-1-independent responses of dendritic cells to anthrax lethal toxin. Cell. Microbiol. 10, 1190-120
114. Reimer, T., Shaw, M. H., Franchi, L., Coban, C., Ishii, K. J., Akira, S., Horii, T., Rodriguez, A., and Nunez, G. (2010). Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome. Eur. J. Immunol. 40, 764-76
115. Ren, T., Zamboni, D. S., Roy, C. R., Dietrich, W. F., and Vance, R. E. (2006). Flagellin-deficient Legionella mutants evade caspase-1and Naip5mediated macrophage immunity. PLoS Pathog. 2, e18. doi:10.1371/journal.ppat.0020018
116. Rodrigue-Gervais, I. G., and Saleh, M. (2010). Genetics of inflammasomeassociated disorders: a lesson in the guiding principals of inflammasome function. Eur. J. Immunol. 40, 643-64
117. Rogers, N. C., Slack, E. C., Edwards, A. D., Nolte, M. A., Schulz, O., Schweighoffer, E., Williams, D. L., Gordon, S., Tybulewicz, V. L., Brown, G. D., and Reis E. Sousa, C. (2005). Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22, 507-51
118. Sachs, J., and Malaney, P. (2002). The economic and social burden of malaria. Nature 415, 680-68
119. Said-Sadier, N., Padilla, E., Langsley, G., and Ojcius, D. M. (2010). Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS ONE 5, e10008. doi:10.1371/journal. pone.0010008
120. Saito, T. and Gale, M. Jr. (2007). Principles of intracellular viral recognition. Curr. Opin. Immunol. 19, 17-2
121. Saleh, M., Mathison, J. C., Wolinski, M. K., Bensinger, S. J., Fitzgerald, P., Droin, N., Ulevitch, R. J., Green, D. R., and Nicholson, D. W. (2006). Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440, 1064-106
122. Saleh, M., and Trinchieri, G. (2011). Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat. Rev. Immunol. 11, 9-2
123. Santic, M., Molmeret, M., Klose, K. E., and Abu Kwaik, Y. (2006). Francisella tularensis travels a novel, twisted road within macrophages. Trends Microbiol. 14, 37-4
124. Sauer, J. D., Witte, C. E., Zemansky, J., Hanson, B., Lauer, P., and Portnoy, D. A. (2010). Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe 7, 412-41
125. Schmitz, N., Kurrer, M., Bachmann, M. F., and Kopf, M. (2005). Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J. Virol. 79, 6441-644
126. Schotte, P., Denecker, G., Van Den Broeke, A., Vandenabeele, P., Cornelis, G. R., and Beyaert, R. (2004). Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta. J. Biol. Chem. 279, 25134-2514
127. Schroder, K., and Tschopp, J. (2010). The inflammasomes. Cell 140, 821-83
128. Shao, W., Yeretssian, G., Doiron, K., Hussain, S. N., and Saleh, M. (2007). The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock. J. Biol. Chem. 282, 36321-3632
129. Shaw, M. H., Reimer, T., Kim, Y. G., and Nunez, G. (2008). NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr. Opin. Immunol. 20, 377-38
130. Shen, A., and Higgins, D. E. (2006). The MogR transcriptional repressor regulates nonhierarchal expression of flagellar motility genes and virulence in Listeria monocytogenes. PLoS Pathog. 2, e30. doi:10.1371/journal. ppat.0020030
131. Shio, M. T., Eisenbarth, S. C., Savaria, M., Vinet, A. F., Bellemare, M. J., Harder, K. W., Sutterwala, F. S., Bohle, D. S., Descoteaux, A., Flavell, R. A., and Olivier, M. (2009). Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog. 5, e1000559. doi:10.1371/ journal.ppat.1000559
132. Silveira, T. N., and Zamboni, D. S. (2010). Pore formation triggered by Legionella spp. is an Nlrc4 inflammasomedependent host cell response that precedes pyroptosis. Infect. Immun. 78, 1403-141
133. Squires, R. C., Muehlbauer, S. M., and Brojatsch, J. (2007). Proteasomes control caspase-1 activation in anthrax lethal toxin-mediated cell killing. J. Biol. Chem. 282, 34260-3426
134. Stasakova, J., Ferko, B., Kittel, C., Sereinig, S., Romanova, J., Katinger, H., and Egorov, A. (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 1beta and 18. J. Gen. Virol. 86, 185-19
135. Stehlik, C., and Dorfleutner, A. (2007). COPs and POPs: modulators of inflammasome activity. J. Immunol. 179, 7993-799
136. Sun, Y. H., Rolan, H. G., and Tsolis, R. M. (2007). Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium. J. Biol. Chem. 282, 33897-3390
137. Sutterwala, F. S., Mijares, L. A., Li, L., Ogura, Y., Kazmierczak, B. I., and Flavell, R. A. (2007). Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 204, 3235-324
138. Suzuki, T., Franchi, L., Toma, C., Ashida, H., Ogawa, M., Yoshikawa, Y., Mimuro, H., Inohara, N., Sasakawa, C., and Nunez, G. (2007). Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 3, e111. doi:10.1371/journal. ppat.0030111
139. Takeuchi, O., and Akira, S. (2010). Pattern recognition receptors and inflammation. Cell 140, 805-82
140. Terra, J. K., Cote, C. K., France, B., Jenkins, A. L., Bozue, J. A., Welkos, S. L., Levine, S. M., and Bradley, K. A. (2010). Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/ Nlrp1b. J. Immunol. 184, 17-2
141. Thomas, P. G., Dash, P., Aldridge, J. R. Jr., Ellebedy, A. H., Reynolds, C., Funk, A. J., Martin, W. J., Lamkanfi, M., Webby, R. J., Boyd, K. L., Doherty, P. C., and Kanneganti, T. D. (2009). The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 30, 566-57
142. Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J., Elliston, K. O., Ayala, J. M., Casano, F. J., Chin, J., Ding, G. J. F., Egger, L. A., Gaffney, E. P., Limjuco, G., Palyha, O. C., Raju, S. M., Rolando, A. M., Salley, J. P., Yamin, T. T., Lee, T. D., Shively, J. E., Maccross, M., Mumford, R. A., Schmidt, J. A., and Tocci, M. J. (1992). A novel heterodimeric cysteine protease is required for interleukin-1beta processing in monocytes. Nature 356, 768-77
143. Tsuchiya, K., Hara, H., Kawamura, I., Nomura, T., Yamamoto, T., Daim, S., Dewamitta, S. R., Shen, Y., Fang, R., and Mitsuyama, M. (2010). Involvement of absent in melanoma 2 in inflammasome activation in macrophages infected with Listeria monocytogenes. J. Immunol. 185, 1186-119
144. Tsuji, N. M., Tsutsui, H., Seki, E., Kuida, K., Okamura, H., Nakanishi, K., and Flavell, R. A. (2004). Roles of caspase-1 in Listeria infection in mice. Int. Immunol. 16, 335-34
145. Ulland, T. K., Buchan, B. W., Ketterer, M. R., Fernandes-Alnemri, T., Meyerholz, D. K., Apicella, M. A., Alnemri, E. S., Jones, B. D., Nauseef, W. M., and Sutterwala, F. S. (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, 2670-267
146. Valdez, Y., Ferreira, R. B. R., and Finlay, B. B. (2009). Molecular mechanisms of Salmonella virulence and host resistance. Curr. Top. Microbiol. 337, 93-12
147. Van De Veerdonk, F. L., Joosten, L. A., Devesa, I., Mora-Montes, H. M., Kanneganti, T. D., Dinarello, C. A., Van Der Meer, J. W., Gow, N. A., Kullberg, B. J., and Netea, M. G. (2009). Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1beta production by the fungal pathogen Candida albicans. J. Infect. Dis. 199, 1087-109
148. Vinzing, M., Eitel, J., Lippmann, J., Hocke, A. C., Zahlten, J., Slevogt, H., N'guessan, P, D., Gunther, S., Schmeck, B., Hippenstiel, S., Flieger, A., Suttorp, N., and Opitz, B. (2008). NAIP and Ipaf control Legionella pneumophila replication in human cells. J. Immunol. 180, 6808-681
149. Vonk, A. G., Netea, M. G., van Krieken, J. H., Iwakura, Y., van der Meer, J. W., and Kullberg, B. J. (2006). Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense against disseminated candidiasis. J. Infect. Dis. 193, 1419-142
150. Walter, K., Holscher, C., Tschopp, J., and Ehlers, S. (2010). NALP3 is not necessary for early protection against experimental tuberculosis. Immunobiology 215, 804-81
151. Wang, S. Y., Miura, M., Jung, Y. K., Zhu, H., Li, E., and Yuan, J. Y. (1998). Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE. Cell 92, 501-50
152. Warren, S. E., Armstrong, A., Hamilton, M. K., Mao, D. P., Leaf, I. A., Miao, E. A., and Aderem, A. (2010). Cutting edge: cytosolic bacterial DNA activates the inflammasome via Aim2. J. Immunol. 185, 818-82
153. Warren, S. E., Mao, D. P., Rodriguez, A. E., Miao, E. A., and Aderem, A. (2008). Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J. Immunol. 180, 7558-756
154. Wickliffe, K. E., Leppla, S. H., and Moayeri, M. (2008). Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome. Cell. Microbiol. 10, 332-34
155. Wright, E. K., Goodart, S. A., Growney, J. D., Hadinoto, V., Endrizzi, M. G., Long, E. M., Sadigh, K., Abney, A. L., Bernstein-Hanley, I., and Dietrich, W. F. (2003). Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila. Curr. Biol. 13, 27-3
156. Wu, J., Fernandes-Alnemri, T., and Alnemri, E. S. (2010). Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J. Clin. Immunol. 30, 693-70
157. Xiang, Y., and Moss, B. (1999). IL-18 binding and inhibition of interferon gamma induction by human poxvirus-encoded proteins. Proc. Natl. Acad. Sci. U.S.A. 96, 11537-1154
158. Zaki, M. H., Boyd, K. L., Vogel, P., Kastan, M. B., Lamkanfi, M., and Kanneganti, T. D. (2010). The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32, 379-39
159. Zamboni, D. S., Kobayashi, K. S., Kohlsdorf, T., Ogura, Y., Long, E. M., Vance, R. E., Kuida, K., Mariathasan, S., Dixit, V. M., Flavell, R. A., Dietrich, W. F., and Roy, C. R. (2006). The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat. Immunol. 7, 318-32
160. Zhou, R., Yazdi, A. S., Menu, P., and Tschopp, J. (2011). A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221-22