NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes

Journal of Experimental Medicine

Volumn 214, Issue 5, 2017, Pages 1351-1370

  Freeman, Leslie ^a   Guo, Haitao ^a   David, Clément N ^a   Brickey, W June ^a   Jha, Sushmita ^a,c   Ting, Jenny P Y ^a,b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

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

^c INDIAN INSTITUTE OF TECHNOLOGY JODHPUR   (India)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 11; CATHEPSIN; CRYOPYRIN; CUPRIZONE; INFLAMMASOME; INTERLEUKIN 1BETA CONVERTING ENZYME; LYSOPHOSPHATIDYLCHOLINE; PROTEIN NLRC4; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; CALCIUM BINDING PROTEIN; IPAF PROTEIN, MOUSE; NLRP3 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTE; ASTROCYTOSIS; CALCIUM MOBILIZATION; CONTROLLED STUDY; DEMYELINATION; HUMAN; HUMAN TISSUE; MALE; MICROGLIA; MOUSE; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; ANIMAL; C57BL MOUSE; DISEASE MODEL; DRUG EFFECTS; INFLAMMATION; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; APOPTOSIS REGULATORY PROTEINS; ASTROCYTES; CALCIUM-BINDING PROTEINS; CUPRIZONE; DISEASE MODELS, ANIMAL; INFLAMMASOMES; INFLAMMATION; LYSOPHOSPHATIDYLCHOLINES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROGLIA; NLR FAMILY, PYRIN DOMAIN-CONTAINING 3 PROTEIN;

EID: 85021662528     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20150237     Document Type: Article

References (96)

1. Adamczak, S.E., J.P. de Rivero Vaccari, G. Dale, F.J. Brand III, D. Nonner, M.R. Bullock, G.P. Dahl, W.D. Dietrich, and R.W. Keane. 2014. Pyroptotic neuronal cell death mediated by the AIM2 inflammasome. J. Cereb. Blood Flow Metab. 34:621-629. http ://dx .doi .org/10 .1038/jcbfm .2013 .236
2. Allen, I.C., E.M. TeKippe, R.M. Woodford, J.M. Uronis, E.K. Holl, A.B. Rogers, H.H. Herfarth, C. Jobin, and J.P. Ting. 2010. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J. Exp. Med. 207:1045-1056. http ://dx .doi .org/10 .1084/jem .20100050
3. Amer, A., L. Franchi, T.D. Kanneganti, M. Body-Malapel, N. Ozören, G. Brady, S. Meshinchi, R. Jagirdar, A. Gewirtz, S. Akira, and G. Núñez. 2006. Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J. Biol. Chem. 281:35217-35223. http ://dx .doi .org/10 .1074/jbc .M604933200
4. Anand, P.K., R.K. Malireddi, J.R. Lukens, P. Vogel, J. Bertin, M. Lamkanfi, and T.D. Kanneganti. 2012. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature. 488:389-393. http ://dx .doi .org/10 .1038/nature11250
5. Arnett, H.A., J. Mason, M. Marino, K. Suzuki, G.K. Matsushima, and J.P. Ting. 2001. TNFa promotes proliferation of oligodendrocyte progenitors and remyelination. Nat. Neurosci. 4:1116-1122. http ://dx .doi .org/10 .1038/nn738
6. Arnett, H.A., R.P. Hellendall, G.K. Matsushima, K. Suzuki, V.E. Laubach, P. Sherman, and J.P. Ting. 2002. The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. J. Immunol. 168:427-433. http ://dx .doi .org/10 .4049/jimmunol .168 .1 .427
7. Bauer, C., P. Duewell, H.A. Lehr, S. Endres, and M. Schnurr. 2012. Protective and aggravating effects of Nlrp3 inflammasome activation in IBD models: influence of genetic and environmental factors. Dig. Dis. 30:82-90. http ://dx .doi .org/10 .1159/000341681
8. Boyden, E.D., and W.F. Dietrich. 2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat. Genet. 38:240-244. http ://dx .doi .org/10 .1038/ng1724
9. Broderick, L., D. De Nardo, B.S. Franklin, H.M. Hoffman, and E. Latz. 2015. The inflammasomes and autoinflammatory syndromes. Annu. Rev. Pathol. 10:395-424. http ://dx .doi .org/10 .1146/annurev-pathol-012414-040431
10. Broz, P., and V.M. Dixit. 2016. Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16:407-420. http ://dx .doi .org/10 .1038/nri .2016 .58
11. Broz, P., J. von Moltke, J.W. Jones, R.E. Vance, and D.M. Monack. 2010. Differential requirement for Caspase-1 autoproteolysis in pathogeninduced cell death and cytokine processing. Cell Host Microbe. 8:471-483. http ://dx .doi .org/10 .1016/j .chom .2010 .11 .007
12. Bürckstümmer, T., C. Baumann, S. Blüml, E. Dixit, G. Dürnberger, H. Jahn, M. Planyavsky, M. Bilban, J. Colinge, K.L. Bennett, and G. Superti-Furga. 2009. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10:266-272. http ://dx .doi .org/10 .1038/ni .1702
13. Canna, S.W., A.A. de Jesus, S. Gouni, S.R. Brooks, B. Marrero, Y. Liu, M.A. DiMattia, K.J. Zaal, G.A. Sanchez, H. Kim, et al. 2014. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat. Genet. 46:1140-1146. http ://dx .doi .org/10 .1038/ng .3089
14. Carson, M.J. 2002. Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia. 40:218-231. http ://dx .doi .org/10 .1002/glia .10145
15. Carvalho, F.A., I. Nalbantoglu, J.D. Aitken, R. Uchiyama, Y. Su, G.H. Doho, M. Vijay-Kumar, and A.T. Gewirtz. 2012. Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges. Mucosal Immunol. 5:288-298. http ://dx .doi .org/10 .1038/mi .2012 .8
16. Codolo, G., N. Plotegher, T. Pozzobon, M. Brucale, I. Tessari, L. Bubacco, and M. de Bernard. 2013. Triggering of inflammasome by aggregated a-synuclein, an inflammatory response in synucleinopathies. PLoS One. 8:e55375. http ://dx .doi .org/10 .1371/journal .pone .0055375
17. Collawn, J.F., and E.N. Benveniste. 1999. Regulation of MHC class II expression in the central nervous system. Microbes Infect. 1:893-902. http ://dx .doi .org/10 .1016/S1286-4579(99)00228-2
18. Davis, B.K., R.A. Roberts, M.T. Huang, S.B. Willingham, B.J. Conti, W.J. Brickey, B.R. Barker, M. Kwan, D.J. Taxman, M.A. Accavitti-Loper, et al. 2011. Cutting edge: NLRC5-dependent activation of the inflammasome. J. Immunol. 186:1333-1337. http ://dx .doi .org/10 .4049/jimmunol .1003111
19. Denes, A., G. Coutts, N. Lénárt, S.M. Cruickshank, P. Pelegrin, J. Skinner, N. Rothwell, S.M. Allan, and D. Brough. 2015. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc. Natl. Acad. Sci. USA. 112:4050-4055. http ://dx .doi .org/10 .1073/pnas .1419090112
20. de Rivero Vaccari, J.P., G. Lotocki, A.E. Marcillo, W.D. Dietrich, and R.W. Keane. 2008. A molecular platform in neurons regulates inflammation after spinal cord injury. J. Neurosci. 28:3404-3414. http ://dx .doi .org/10 .1523/JNE URO SCI .0157-08 .2008
21. de Rivero Vaccari, J.P., G. Lotocki, O.F. Alonso, H.M. Bramlett, W.D. Dietrich, and R.W. Keane. 2009. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J. Cereb. Blood Flow Metab. 29:1251-1261. http ://dx .doi .org/10 .1038/jcbfm .2009 .46
22. Diebolder, C.A., E.F. Halff, A.J. Koster, E.G. Huizinga, and R.I. Koning. 2015. Cryoelectron tomography of the NAIP5/NLRC4 inflammasome: Implications for NLR activation. Structure. 23:2349-2357. http ://dx .doi .org/10 .1016/j .str .2015 .10 .001
23. Dong, Y., and E.N. Benveniste. 2001. Immune function of astrocytes. Glia. 36:180-190. http ://dx .doi .org/10 .1002/glia .1107
24. Duncan, J.A., D.T. Bergstralh, Y. Wang, S.B. Willingham, Z. Ye, A.G. Zimmermann, and J.P. Ting. 2007. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc. Natl. Acad. Sci. USA. 104:8041-8046. http ://dx .doi .org/10 .1073/pnas .0611496104
25. Elinav, E., T. Strowig, A.L. Kau, J. Henao-Mejia, C.A. Thaiss, C.J. Booth, D.R. Peaper, J. Bertin, S.C. Eisenbarth, J.I. Gordon, and R.A. Flavell. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 145:745-757. http ://dx .doi .org/10 .1016/j .cell .2011 .04 .022
26. Farooqui, A.A., W.Y. Ong, and L.A. Horrocks. 2006. Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol. Rev. 58:591-620. http ://dx .doi .org/10 .1124/pr .58 .3 .7
27. Fernandes-Alnemri, T., J.W. Yu, P. Datta, J. Wu, and E.S. Alnemri. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 458:509-513. http ://dx .doi .org/10 .1038/nature07710
28. Franchi, L., A. Amer, M. Body-Malapel, T.D. Kanneganti, N. Ozören, R. Jagirdar, N. Inohara, P. Vandenabeele, J. Bertin, A. Coyle, et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat. Immunol. 7:576-582. http ://dx .doi .org/10 .1038/ni1346
29. Franchi, L., R. Muñoz-Planillo, T. Reimer, T. Eigenbrod, and G. Núñez. 2010. Inflammasomes as microbial sensors. Eur. J. Immunol. 40:611-615. http ://dx .doi .org/10 .1002/eji .200940180
30. Franco-Pons, N., M. Torrente, M.T. Colomina, and E. Vilella. 2007. Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination. Toxicol. Lett. 169:205-213. http ://dx .doi .org/10 .1016/j .toxlet .2007 .01 .010
31. Freeman, L.C., and J.P. Ting. 2016. The pathogenic role of the inflammasome in neurodegenerative diseases. J. Neurochem. 136:29-38. http ://dx .doi .org/10 .1111/jnc .13217
32. Geddes, B.J., L. Wang, W.J. Huang, M. Lavellee, G.A. Manji, M. Brown, M. Jurman, J. Cao, J. Morgenstern, S. Merriam, et al. 2001. Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis. Biochem. Biophys. Res. Commun. 284:77-82. http ://dx .doi .org/10 .1006/bbrc .2001 .4928
33. Guo, H., J.B. Callaway, and J.P. Ting. 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 21:677-687. http ://dx .doi .org/10 .1038/nm .3893
34. Halff, E.F., C.A. Diebolder, M. Versteeg, A. Schouten, T.H. Brondijk, and E.G. Huizinga. 2012. Formation and structure of a NAIP5-NLRC4 inflammasome induced by direct interactions with conserved N-and C-terminal regions of flagellin. J. Biol. Chem. 287:38460-38472. http ://dx .doi .org/10 .1074/jbc .M112 .393512
35. Halle, A., V. Hornung, G.C. Petzold, C.R. Stewart, B.G. Monks, T. Reinheckel, K.A. Fitzgerald, E. Latz, K.J. Moore, and D.T. Golenbock. 2008. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat. Immunol. 9:857-865. http ://dx .doi .org/10 .1038/ni .1636
36. Hanisch, U.K., and H. Kettenmann. 2007. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10:1387-1394. http ://dx .doi .org/10 .1038/nn1997
37. Heneka, M.T., M.K. O'Banion, D. Terwel, and M.P. Kummer. 2010. Neuroinflammatory processes in Alzheimer's disease. J. Neural Transm. (Vienna). 117:919-947. http ://dx .doi .org/10 .1007/s00702-010-0438-z
38. Heneka, M.T., M.P. Kummer, A. Stutz, A. Delekate, S. Schwartz, A. Vieira-Saecker, A. Griep, D. Axt, A. Remus, T.C. Tzeng, et al. 2013. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature. 493:674-678. http ://dx .doi .org/10 .1038/nature11729
39. Hiremath, M.M., Y. Saito, G.W. Knapp, J.P. Ting, K. Suzuki, and G.K. Matsushima. 1998. Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice. J. Neuroimmunol. 92:38-49. http ://dx .doi .org/10 .1016/S0165-5728(98)00168-4
40. Hornung, V., A. Ablasser, M. Charrel-Dennis, F. Bauernfeind, G. Horvath, D.R. Caffrey, E. Latz, and K.A. Fitzgerald. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 458:514-518. http ://dx .doi .org/10 .1038/nature07725
41. Hu, B., E. Elinav, S. Huber, C.J. Booth, T. Strowig, C. Jin, S.C. Eisenbarth, and R.A. Flavell. 2010. Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4. Proc. Natl. Acad. Sci. USA. 107:21635-21640. http ://dx .doi .org/10 .1073/pnas .1016814108
42. Hu, Z., Q. Zhou, C. Zhang, S. Fan, W. Cheng, Y. Zhao, F. Shao, H.W. Wang, S.F. Sui, and J. Chai. 2015. Structural and biochemical basis for induced self-propagation of NLRC4. Science. 350:399-404. http ://dx .doi .org/10 .1126/science .aac5489
43. Ikeda, K., K. Yamaguchi, T. Tanaka, Y. Mizuno, A. Hijikata, O. Ohara, H. Takada, K. Kusuhara, and T. Hara. 2010. Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease. Clin. Exp. Immunol. 160:246-255. http ://dx .doi .org/10 .1111/j .1365-2249 .2009 .04073 .x
44. Jha, S., S.Y. Srivastava, W.J. Brickey, H. Iocca, A. Toews, J.P. Morrison, V.S. Chen, D. Gris, G.K. Matsushima, and J.P. Ting. 2010. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J. Neurosci. 30:15811-15820. http ://dx .doi .org/10 .1523/JNE URO SCI .4088-10 .2010
45. Kabarowski, J.H., Y. Xu, and O.N. Witte. 2002. Lysophosphatidylcholine as a ligand for immunoregulation. Biochem. Pharmacol. 64:161-167. http ://dx .doi .org/10 .1016/S0006-2952(02)01179-6
46. Kanneganti, T.D., N. Ozören, M. Body-Malapel, A. Amer, J.H. Park, L. Franchi, J. Whitfield, W. Barchet, M. Colonna, P. Vandenabeele, et al. 2006. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature. 440:233-236. http ://dx .doi .org/10 .1038/nature04517
47. Keller, M., A. Rüegg, S. Werner, and H.D. Beer. 2008. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 132:818-831. http ://dx .doi .org/10 .1016/j .cell .2007 .12 .040
48. Khare, S., A. Dorfleutner, N.B. Bryan, C. Yun, A.D. Radian, L. de Almeida, Y. Rojanasakul, and C. Stehlik. 2012. An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity. 36:464-476. http ://dx .doi .org/10 .1016/j .immuni .2012 .02 .001
49. Kigerl, K.A., J.P. de Rivero Vaccari, W.D. Dietrich, P.G. Popovich, and R.W. Keane. 2014. Pattern recognition receptors and central nervous system repair. Exp. Neurol. 258:5-16. http ://dx .doi .org/10 .1016/j .expneurol .2014 .01 .001
50. Kofoed, E.M., and R.E. Vance. 2011. Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature. 477:592-595. http ://dx .doi .org/10 .1038/nature10394
51. Kolb, R., L. Phan, N. Borcherding, Y. Liu, F. Yuan, A.M. Janowski, Q. Xie, K.R. Markan, W. Li, M.J. Potthoff, et al. 2016. Obesity-associated NLRC4 inflammasome activation drives breast cancer progression. Nat. Commun. 7:13007. http ://dx .doi .org/10 .1038/ncomms13007
52. Lin, P., and R.D. Ye. 2003. The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis. J. Biol. Chem. 278:14379-14386. http ://dx .doi .org/10 .1074/jbc .M209101200
53. Liu, L., and C. Chan. 2014. IPAF inflammasome is involved in interleukin-1β production from astrocytes, induced by palmitate; implications for Alzheimer's Disease. Neurobiol. Aging. 35:309-321. http ://dx .doi .org/10 .1016/j .neurobiolaging .2013 .08 .016
54. Liu, L., A. Belkadi, L. Darnall, T. Hu, C. Drescher, A.C. Cotleur, D. Padovani-Claudio, T. He, K. Choi, T.E. Lane, et al. 2010. CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis. Nat. Neurosci. 13:319-326. http ://dx .doi .org/10 .1038/nn .2491
55. Ma, A., D.L. Boone, and J.P. Lodolce. 2000. The pleiotropic functions of interleukin 15. J. Exp. Med. 191:753-756. http ://dx .doi .org/10 .1084/jem .191 .5 .753
56. Macaluso, F., M. Nothnagel, Q. Parwez, E. Petrasch-Parwez, F.G. Bechara, J.T. Epplen, and S. Hoffjan. 2007. Polymorphisms in NAC HT-LRR (NLR) genes in atopic dermatitis. Exp. Dermatol. 16:692-698. http ://dx .doi .org/10 .1111/j .1600-0625 .2007 .00589 .x
57. Man, S.M., L.J. Hopkins, E. Nugent, S. Cox, I.M. Glück, P. Tourlomousis, J.A. Wright, P. Cicuta, T.P. Monie, and C.E. Bryant. 2014. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc. Natl. Acad. Sci. USA. 111:7403-7408. http ://dx .doi .org/10 .1073/pnas .1402911111
58. Mariathasan, S., K. Newton, D.M. Monack, D. Vucic, D.M. French, W.P. Lee, M. Roose-Girma, S. Erickson, and V.M. Dixit. 2004. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 430:213-218. http ://dx .doi .org/10 .1038/nature02664
59. Mariathasan, S., D.S. Weiss, K. Newton, J. McBride, K. O'Rourke, M. Roose-Girma, W.P. Lee, Y. Weinrauch, D.M. Monack, and V.M. Dixit. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 440:228-232. http ://dx .doi .org/10 .1038/nature04515
60. Martinon, F., K. Burns, and J. Tschopp. 2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell. 10:417-426. http ://dx .doi .org/10 .1016/S1097-2765(02)00599-3
61. Martinon, F., V. Pétrilli, A. Mayor, A. Tardivel, and J. Tschopp. 2006. Goutassociated uric acid crystals activate the NALP3 inflammasome. Nature. 440:237-241. http ://dx .doi .org/10 .1038/nature04516
62. Matsushima, G.K., and P. Morell. 2001. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 11:107-116. http ://dx .doi .org/10 .1111/j .1750-3639 .2001 .tb00385 .x
63. McCarthy, K.D., and J. de Vellis. 1980. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85:890-902. http ://dx .doi .org/10 .1083/jcb .85 .3 .890
64. Miao, E.A., C.M. Alpuche-Aranda, M. Dors, A.E. Clark, M.W. Bader, S.I. Miller, and A. Aderem. 2006. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nat. Immunol. 7:569-575. http ://dx .doi .org/10 .1038/ni1344
65. Miao, E.A., D.P. Mao, N. Yudkovsky, R. Bonneau, C.G. Lorang, S.E. Warren, I.A. Leaf, and A. Aderem. 2010. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc. Natl. Acad. Sci. USA. 107:3076-3080. http ://dx .doi .org/10 .1073/pnas .0913087107
66. Molofsky, A.V., R. Krencik, E.M. Ullian, H.-H. Tsai, B. Deneen, W.D. Richardson, B.A. Barres, and D.H. Rowitch. 2012. Astrocytes and disease: a neurodevelopmental perspective. Genes Dev. 26:891-907. http ://dx .doi .org/10 .1101/gad .188326 .112
67. Napoli, I., and H. Neumann. 2009. Microglial clearance function in health and disease. Neuroscience. 158:1030-1038. http ://dx .doi .org/10 .1016/j .neuroscience .2008 .06 .046
68. Plant, S.R., H.A. Iocca, Y. Wang, J.C. Thrash, B.P. O'Connor, H.A. Arnett, Y.X. Fu, M.J. Carson, and J.P. Ting. 2007. Lymphotoxin beta receptor (LtβR): dual roles in demyelination and remyelination and successful therapeutic intervention using LtβR-Ig protein. J. Neurosci. 27:7429-7437. http ://dx .doi .org/10 .1523/JNE URO SCI .1307-07 .2007
69. Poyet, J.L., S.M. Srinivasula, M. Tnani, M. Razmara, T. Fernandes-Alnemri, and E.S. Alnemri. 2001. Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J. Biol. Chem. 276:28309-28313. http ://dx .doi .org/10 .1074/jbc .C100250200
70. Qu, Y., S. Misaghi, K. Newton, A. Maltzman, A. Izrael-Tomasevic, D. Arnott, and V.M. Dixit. 2016. NLRP3 recruitment by NLRC4 during Salmonella infection. J. Exp. Med. 213:877-885. http ://dx .doi .org/10 .1084/jem .20132234
71. Rathinam, V.A., Z. Jiang, S.N. Waggoner, S. Sharma, L.E. Cole, L. Waggoner, S.K. Vanaja, B.G. Monks, S. Ganesan, E. Latz, et al. 2010. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11:395-402. http ://dx .doi .org/10 .1038/ni .1864
72. Rayamajhi, M., D.E. Zak, J. Chavarria-Smith, R.E. Vance, and E.A. Miao. 2013. Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein. J. Immunol. 191:3986-3989. http ://dx .doi .org/10 .4049/jimmunol .1301549
73. Rikitake, Y., K. Hirata, T. Yamashita, K. Iwai, S. Kobayashi, H. Itoh, M. Ozaki, J. Ejiri, M. Shiomi, N. Inoue, et al. 2002. Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques. Arterioscler. Thromb. Vasc. Biol. 22:2049-2053. http ://dx .doi .org/10 .1161/01 .ATV .0000040598 .18570 .54
74. Rivest, S. 2009. Regulation of innate immune responses in the brain. Nat. Rev. Immunol. 9:429-439. http ://dx .doi .org/10 .1038/nri2565
75. Rock, K.L., E. Latz, F. Ontiveros, and H. Kono. 2010. The sterile inflammatory response. Annu. Rev. Immunol. 28:321-342. http ://dx .doi .org/10 .1146/annurev-immunol-030409-101311
76. Schilling, T., F. Lehmann, B. Rückert, and C. Eder. 2004. Physiological mechanisms of lysophosphatidylcholine-induced de-ramification of murine microglia. J. Physiol. 557:105-120. http ://dx .doi .org/10 .1113/jphysiol .2004 .060632
77. Schneider, C.A., W.S. Rasband, and K.W. Eliceiri. 2012. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 9:671-675. http ://dx .doi .org/10 .1038/nmeth .2089
78. Shao, W., G. Yeretssian, K. Doiron, S.N. Hussain, and M. Saleh. 2007. The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock. J. Biol. Chem. 282:36321-36329. http ://dx .doi .org/10 .1074/jbc .M708182200
79. Sheikh, A.M., and A. Nagai. 2011. Lysophosphatidylcholine modulates fibril formation of amyloid beta peptide. FEBS J. 278:634-642. http ://dx .doi .org/10 .1111/j .1742-4658 .2010 .07984 .x
80. Shikishima, K., A. Mizuno, K. Kawai, and H. Matsuzaki. 1985. Focal experimental demyelination in monkey optic nerve by lysophosphatidylcholine. Jpn. J. Ophthalmol. 29:429-433
81. Stock, C., T. Schilling, A. Schwab, and C. Eder. 2006. Lysophosphatidylcholine stimulates IL-1β release from microglia via a P2X7 receptor-independent mechanism. J. Immunol. 177:8560-8568. http ://dx .doi .org/10 .4049/jimmunol .177 .12 .8560
82. Strowig, T., J. Henao-Mejia, E. Elinav, and R. Flavell. 2012. Inflammasomes in health and disease. Nature. 481:278-286. http ://dx .doi .org/10 .1038/nature10759
83. Stüve, O., S. Youssef, A.J. Slavin, C.L. King, J.C. Patarroyo, D.L. Hirschberg, W.J. Brickey, J.M. Soos, J.F. Piskurich, H.A. Chapman, and S.S. Zamvil. 2002. The role of the MHC class II transactivator in class II expression and antigen presentation by astrocytes and in susceptibility to central nervous system autoimmune disease. J. Immunol. 169:6720-6732. http ://dx .doi .org/10 .4049/jimmunol .169 .12 .6720
84. Sutterwala, F.S., Y. Ogura, M. Szczepanik, M. Lara-Tejero, G.S. Lichtenberger, E.P. Grant, J. Bertin, A.J. Coyle, J.E. Galán, P.W. Askenase, and R.A. Flavell. 2006. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 24:317-327. http ://dx .doi .org/10 .1016/j .immuni .2006 .02 .004
85. Sutterwala, F.S., L.A. Mijares, L. Li, Y. Ogura, B.I. Kazmierczak, and R.A. Flavell. 2007. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 204:3235-3245. http ://dx .doi .org/10 .1084/jem .20071239
86. Suzuki, T., L. Franchi, C. Toma, H. Ashida, M. Ogawa, Y. Yoshikawa, H. Mimuro, N. Inohara, C. Sasakawa, and G. Nuñez. 2007. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 3:e111. http ://dx .doi .org/10 .1371/journal .ppat .0030111
87. Ting, J.P., and B.K. Davis. 2005. CAT ERP ILL ER: a novel gene family important in immunity, cell death, and diseases. Annu. Rev. Immunol. 23:387-414. http ://dx .doi .org/10 .1146/annurev .immunol .23 .021704 .115616
88. Triantafilou, K., S. Kar, F.J. van Kuppeveld, and M. Triantafilou. 2013. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. Am. J. Respir. Cell Mol. Biol. 49:923-934. http ://dx .doi .org/10 .1165/rcmb .2013-0032OC
89. Vereyken, E.J., D.M. Fluitsma, M.J. Bolijn, C.D. Dijkstra, and C.E. Teunissen. 2009. An in vitro model for de-and remyelination using lysophosphatidyl choline in rodent whole brain spheroid cultures. Glia. 57:1326-1340. http ://dx .doi .org/10 .1002/glia .20852
90. Vladimer, G.I., D. Weng, S.W. Paquette, S.K. Vanaja, V.A. Rathinam, M.H. Aune, J.E. Conlon, J.J. Burbage, M.K. Proulx, Q. Liu, et al. 2012. The NLRP12 inflammasome recognizes Yersinia pestis. Immunity. 37:96-107. http ://dx .doi .org/10 .1016/j .immuni .2012 .07 .006
91. Waxman, S.G., J.D. Kocsis, and K.C. Nitta. 1979. Lysophosphatidyl cholineinduced focal demyelination in the rabbit corpus callosum. Lightmicroscopic observations. J. Neurol. Sci. 44:45-53. http ://dx .doi .org/10 .1016/0022-510X(79)90221-1
92. Wu, J., S. Yoo, D. Wilcock, J.M. Lytle, P.Y. Leung, C.A. Colton, and J.R. Wrathall. 2010. Interaction of NG2+ glial progenitors and microglia/macrophages from the injured spinal cord. Glia. 58:410-422
93. Wyss-Coray, T. 2006. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med. 12:1005-1015
94. Yang, J., Y. Zhao, J. Shi, and F. Shao. 2013. Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation. Proc. Natl. Acad. Sci. USA. 110:14408-14413. http ://dx .doi .org/10 .1073/pnas .1306376110
95. Zhang, L., S. Chen, J. Ruan, J. Wu, A.B. Tong, Q. Yin, Y. Li, L. David, A. Lu, W.L. Wang, et al. 2015. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science. 350:404-409. http ://dx .doi .org/10 .1126/science .aac5789
96. Zhao, Y., J. Yang, J. Shi, Y.N. Gong, Q. Lu, H. Xu, L. Liu, and F. Shao. 2011. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature. 477:596-600. http ://dx .doi .org/10 .1038/nature10510