The inflammasomes: mechanisms of activation and function

Current Opinion in Immunology

Volumn 22, Issue 1, 2010, Pages 28-33

  Latz, Eicke ^a,b  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ABSENT IN MELANOMA 2; ADENOSINE TRIPHOSPHATE; CASPASE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CASPASE RECRUITMENT DOMAIN PROTEIN 4; CRYOPYRIN; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; MYELOID DIFFERENTIATION FACTOR 88; NUCLEOTIDE BINDING PROTEIN; PROTEIN NLRCC1; PROTEIN NLRCC4; PROTEIN PYHIN; UNCLASSIFIED DRUG;

AUTOIMMUNE DISEASE; AUTOREGULATION; BACTERIAL INFECTION; CELL ACTIVATION; CYTOKINE RELEASE; DOWN REGULATION; GENE ACTIVATION; INFLAMMATORY DISEASE; LUPUS ERYTHEMATOSUS; NONHUMAN; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; CASPASE 1; HUMANS; INFLAMMATION; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; INTERLEUKIN-1BETA; PROTEIN BINDING; SIGNAL TRANSDUCTION;

EID: 77249118801     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2009.12.004     Document Type: Review

References (40)

1. Takeda K., Kaisho T., and Akira S. Toll-like receptors. Annu Rev Immunol 21 (2003) 335-376
2. Martinon F., Mayor A., and Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol 27 (2009) 229-265
3. 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., et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356 (1992) 768-774
4. Duncan J.A., Bergstralh D.T., Wang Y., Willingham S.B., Ye Z., Zimmermann A.G., and Ting J.P. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc Natl Acad Sci U S A 104 (2007) 8041-8046. First description of ATP binding to NLRP3 and the functional relevance for NLRP3 activation.
5. Ting J.P., Lovering R.C., Alnemri E.S., Bertin J., Boss J.M., Davis B.K., Flavell R.A., Girardin S.E., Godzik A., Harton J.A., et al. The NLR gene family: a standard nomenclature. Immunity 28 (2008) 285-287
6. Martinon F., Burns K., and Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10 (2002) 417-426. First biochemical characterization of the NLRP1 multiprotein complex and introduction of the name 'inflammasome'.
7. Faustin B., Lartigue L., Bruey J.M., Luciano F., Sergienko E., Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., and Reed J.C. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25 (2007) 713-724. This paper reveals that MDP is a ligand for the NLRP1 inflammasome in an in vitro reconstitution assay.
8. Boyden E.D., and Dietrich W.F. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38 (2006) 240-244
9. Sutterwala F.S., and Flavell R.A. NLRC4/IPAF: a CARD carrying member of the NLR family. Clin Immunol 130 (2009) 2-6
10. 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., et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem 281 (2006) 36560-36568
11. Muruve D.A., Petrilli V., Zaiss A.K., White L.R., Clark S.A., Ross P.J., Parks R.J., and Tschopp J. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452 (2008) 103-107
12. Duncan J.A., Gao X., Huang M.T., O'Connor B.P., Thomas C.E., Willingham S.B., Bergstralh D.T., Jarvis G.A., Sparling P.F., and Ting J.P. Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. J Immunol 182 (2009) 6460-6469
13. Griffith J.W., Sun T., McIntosh M.T., and Bucala R. Pure hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid. J Immunol 183 (2009) 5208-5220
14. Dostert C., Guarda G., Romero J.F., Menu P., Gross O., Tardivel A., Suva M.L., Stehle J.C., Kopf M., Stamenkovic I., et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS ONE 4 (2009) e6510
15. Gross O., Poeck H., Bscheider M., Dostert C., Hannesschlager N., Endres S., Hartmann G., Tardivel A., Schweighoffer E., Tybulewicz V., et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459 (2009) 433-436
16. Hise A.G., Tomalka J., Ganesan S., Patel K., Hall B.A., Brown G.D., and Fitzgerald K.A. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 5 (2009) 487-497
17. Dostert C., Petrilli V., Van Bruggen R., Steele C., Mossman B.T., and Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320 (2008) 674-677. Introduction of the ROS theory of NLRP3 inflammasome activation.
18. Martinon F., Petrilli V., Mayor A., Tardivel A., and Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440 (2006) 237-241. This study first demonstrates that crystals can activate the NLRP3 inflammasome.
19. 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. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9 (2008) 857-865. This paper implicates the NLRP3 inflammasome into neurodegeneration in response to aggregated Abeta peptides.
20. Hornung V., Bauernfeind F., Halle A., Samstad E.O., Kono H., Rock K.L., Fitzgerald K.A., and Latz E. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9 (2008) 847-856. This paper demonstrated that lysosomal cathepsins act upstream of the NLRP3 inflammasome.
21. Mariathasan S., Weiss D.S., Newton K., McBride J., O'Rourke K., Roose-Girma M., Lee W.P., Weinrauch Y., Monack D.M., and Dixit V.M. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440 (2006) 228-232. Recognition of the molecular mechanisms of ATP induced IL-1b secretion.
22. Li H., Ambade A., and Re F. Cutting edge: necrosis activates the NLRP3 inflammasome. J Immunol 183 (2009) 1528-1532
23. Petrilli V., Papin S., Dostert C., Mayor A., Martinon F., and Tschopp J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ 14 (2007) 1583-1589
24. Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G., Caffrey D.R., Latz E., and Fitzgerald K.A. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458 (2009) 514-518
25. Burckstummer T., Baumann C., Bluml S., Dixit E., Durnberger G., Jahn H., Planyavsky M., Bilban M., Colinge J., Bennett K.L., et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol 10 (2009) 266-272
26. Fernandes-Alnemri T., Yu J.W., Datta P., Wu J., and Alnemri E.S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458 (2009) 509-513
27. Roberts T.L., Idris A., Dunn J.A., Kelly G.M., Burnton C.M., Hodgson S., Hardy L.L., Garceau V., Sweet M.J., Ross I.L., et al. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323 (2009) 1057-1060
28. Keller M., Ruegg A., Werner S., and Beer H.D. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132 (2008) 818-831
29. Kroemer G., Galluzzi L., Vandenabeele P., Abrams J., Alnemri E.S., Baehrecke E.H., Blagosklonny M.V., El-Deiry W.S., Golstein P., Green D.R., et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16 (2009) 3-11
30. Dinarello C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27 (2009) 519-550
31. Franchi L., Eigenbrod T., and Nunez G. Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 183 (2009) 792-796
32. Bauernfeind F.G., Horvath G., Stutz A., Alnemri E.S., MacDonald K., Speert D., Fernandes-Alnemri T., Wu J., Monks B.G., Fitzgerald K.A., et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 183 (2009) 787-791. This work demonstrates that priming upregulates NLRP3 expression and enables NLRP3 inflammasome activation.
33. O'Connor Jr. W., Harton J.A., Zhu X., Linhoff M.W., and Ting J.P. Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties. J Immunol 171 (2003) 6329-6333
34. 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. The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci U S A 105 (2008) 9035-9040
35. Meissner F., Molawi K., and Zychlinsky A. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9 (2008) 866-872. This paper indicates that increased ROS inhibit caspase-1 activity by covalent modification.
36. Hauck P., Thilmony R., and He S.Y. A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants. Proc Natl Acad Sci U S A 100 (2003) 8577-8582
37. Chisholm S.T., Coaker G., Day B., and Staskawicz B.J. Host-microbe interactions: shaping the evolution of the plant immune response. Cell 124 (2006) 803-814
38. Dangl J.L., and Jones J.D. Plant pathogens and integrated defence responses to infection. Nature 411 (2001) 826-833
39. Masters S.L., Simon A., Aksentijevich I., and Kastner D.L. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol 27 (2009) 621-668
40. Ghiringhelli F., Apetoh L., Tesniere A., Aymeric L., Ma Y., Ortiz C., Vermaelen K., Panaretakis T., Mignot G., Ullrich E., et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15 (2009) 1170-1178. This study first demonstrates NLRP3 function in tumor defense.