NALP3: a key player in caspase-1 activation

Abstract

The NLR (NACHT-LRR) family of proteins have been implicated in the regulation of immune responses and cell death pathways. Some NLR family members can form multiprotein complexes, called inflammasomes, involved in the activation of pro-inflammatory caspases. Mutations in the NALP3/CIAS1/cryopyrin gene, a member of the NLR family, are linked to three auto-inflammatory disorders: Muckle-Wells syndrome, familial cold auto-inflammatory syndrome and neonatal-onset multisystem inflammatory disease. NALP3 along with the adaptor molecule ASC activates caspase-1 in response to a wide variety of stimuli. Here we review recent findings on the biology of NALP3 suggesting that it has functions beyond that of pathogen recognition.

Keywords

Caspase-1 innate immunity interleukin-1β macrophages NACHT-LRR (NLR)

References

Martinon F. , Tschopp J. NLRs join TLRs as innate sensors of pathogens. Trends Immunol 2005; 26: 447—454.

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

Inohara N. , Chamaillard M. , McDonald C, Núñez G. NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 2005; 74: 355—383.

Martinon F. , Burns K. , Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell 2002; 10: 417—426.

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

Masumoto J. , Taniguchi S. , Ayukawa K. et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J Biol Chem 1999; 274: 33835—33838.

Conway KE , McConnell BB , Bowring CE , Donald CD , Warren ST , Vertino PM TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. Cancer Res 2000; 60: 6236—6242.

Srinivasula SM , Poyet JL , Razmara M. , Datta P. , Zhang Z. , Alnemri ES The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 2002; 277: 19—22.

Stehlik C. , Lee SH , Dorfleutner A. , Stassinopoulos A. , Sagara J. , Reed JC Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation. J. Immunol 2003; 171: 6154—6163.

10.

Wang L. , Manji GA , Grenier JM et al. PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-κB and caspase-1-dependent cytokine processing. J Biol Chem 2002; 277: 29874—29880.

11.

Mariathasan S. , Newton K. , Monack DM et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004; 430: 213—218.

12.

Yamamoto M. , Yaginuma K. , Tsutsui H. et al. ASC is essential for LPS-induced activation of procaspase-1 independently of TLRassociated signal adaptor molecules. Genes Cells 2004; 9: 1055—1067.

13.

Sutterwala FS , Ogura Y. , Szczepanik M. et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 2006; 24: 317—327.

14.

Mariathasan S. , Weiss DS , Newton K. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 2006 ; 440: 228—232.

15.

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

16.

Kanneganti TD , Ozoren N. , Body-Malapel M. et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 2006; 440: 233—236.

17.

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

18.

Ting JP , Kastner DL , Hoffman HM CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 2006; 6: 183—195.

19.

Dowds TA , Masumoto J. , Zhu L. , Inohara N. , Nunez G. Cryopyrin-induced interleukin 1β secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem 2004; 279: 21924—21928.

20.

Stack JH , Beaumont K. , Larsen PD et al. IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients. J Immunol 2005; 175: 2630—2634.

21.

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

22.

Hoffman HM , Rosengren S. , Boyle DL et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 2004; 364: 1779—1785.

23.

Stehlik C. , Fiorentino L. , Dorfleutner A. et al. The PAAD/PYRINfamily protein ASC is a dual regulator of a conserved step in nuclear factor κB activation pathways. J Exp Med 2002; 196: 1605—1615.

24.

O'Connor Jr W. , Harton JA , Zhu X. , Linhoff MW , Ting JP CIAS 1/cryopyrin/PYPAF 1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties . J Immunol 2003; 171: 6329—6333.

25.

Perregaux D. , Gabel CA Interleukin-1β maturation and release in response to ATP and nigericin. J Biol Chem 1994; 269: 15195—15203.

26.

Hogquist KA , Unanue ER , Chaplin DD Release of IL-1 from mononuclear phagocytes . J Immunol 1991; 147: 2181—2186.

27.

Griffiths RJ , Stam EJ , Downs JT , Otterness IG ATP induces the release of IL-1 from LPS-primed cells in vivo. J Immunol 1995; 154: 2821—2828.

28.

Ferrari D. , Pizzirani C. , Adinolfi E. et al. The P2X7 receptor: a key player in IL-1 processing and release . J Immunol 2006; 176: 3877—3883.

29.

Cheneval D. , Ramage P. , Kastelic T. et al. Increased mature interleukin-1β (IL-1β) secretion from THP-1 cells induced by nigericin is a result of activation of p45 IL-1β-converting enzyme processing. J Biol Chem 1998; 273: 17846—17851.

30.

Solle M. , Labasi J. , Perregaux DG et al. Altered cytokine production in mice lacking P2X7 receptors. J Biol Chem 2001; 276: 125—132.

31.

Ferrari D. , Villalba M. , Chiozzi P. , Falzoni S. , Ricciardi-Castagnoli P. , Di Virgilio F. Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. J Immunol 1996; 156: 1531—1539.

32.

Ferrari D. , Chiozzi P. , Falzoni S. et al. Extracellular ATP triggers IL-1β release by activating the purinergic P2Z receptor of human macrophages. J Immunol 1997; 159: 1451—1458.

33.

Walev I. , Reske K. , Palmer M. , Valeva A. , Bhakdi S. Potassium-inhibited processing of IL-1β in human monocytes. EMBO J 1995; 14: 1607—1614.

34.

Sluyter R. , Shemon AN , Wiley JS Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1β release from human monocytes. J Immunol 2004 ; 172: 3399—3405.

35.

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

36.

Hueffer K. , Galán JE Salmonella-induced macrophage death: multiple mechanisms, different outcomes . Cell Microbiol 2004; 6: 1019—1025.

37.

Chen Y. , Smith MR , Thirumalai K. , Zychlinsky A. A bacterial invasin induces macrophage apoptosis by binding directly to ICE . EMBO J 1996; 15: 3853—3860.

38.

Zamboni DS , Kobayashi KS , Kohlsdorf T. et al. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunol 2006; 7: 318—325.

39.

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

40.

Hersh D. , Monack DM , Smith MR , Ghori N. , Falkow S. , Zychlinsky A. The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1 . Proc Natl Acad Sci USA 1999; 96: 2396—2401.

41.

Lara-Tejero M. , Sutterwala FS , Ogura Y. et al. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med 2006; 203:1407—1412.

42.

Monack DM , Hersh D. , Ghori N. , Bouley D. , Zychlinsky A. , Falkow S. Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model. J Exp Med 2000; 192: 249—258.

43.

Rosengren S. , Hoffman HM , Bugbee W. , Boyle DL Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis 2005; 64: 708—714.

44.

Enk AH , Angeloni VL , Udey MC , Katz SI An essential role for Langerhans cell-derived IL-1β in the initiation of primary immune responses in skin. J Immunol 1993; 150: 3698—3704.

45.

Shornick LP , De Togni P. , Mariathasan S. et al. Mice deficient in IL-1β manifest impaired contact hypersensitivity to trinitrochlorobenzone. J Exp Med 1996; 183: 1427—1436.

46.

Shornick LP , Bisarya AK , Chaplin DD IL-1β is essential for Langerhans cell activation and antigen delivery to the lymph nodes during contact sensitization: evidence for a dermal source of IL-1β. Cell Immunol 2001; 211: 105—112.

47.

Sutterwala FS , Noel GJ , Clynes R. , Mosser DM Selective suppression of interleukin-12 induction after macrophage receptor ligation. J Exp Med 1997; 185: 1977—1985.