Inflammasomes and the microbiota—partners in the preservation of mucosal homeostasis

Seminars in Immunopathology

Volumn 37, Issue 1, 2015, Pages 39-46

  Levy, Maayan ^a   Thaiss, Christoph A ^a   Katz, Meirav N ^a   Suez, Jotham ^a   Elinav, Eran ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Colitis; Inflammasome; Microbiota; NLRs

Indexed keywords

CRYOPYRIN; INFLAMMASOME; PROTEIN NLRC; PROTEIN NLRP12; PROTEIN NLRP6; UNCLASSIFIED DRUG;

BIOGEOGRAPHY; COLITIS; COMMENSAL; DYSBIOSIS; HOST PATHOGEN INTERACTION; HOST RESISTANCE; HUMAN; INTESTINE FLORA; METABOLIC SYNDROME X; MUCOSAL IMMUNITY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SPECIES COMPOSITION; HOMEOSTASIS; IMMUNOLOGY; INNATE IMMUNITY; MICROFLORA; SYMBIOSIS;

HOMEOSTASIS; HUMANS; IMMUNITY, INNATE; INFLAMMASOMES; MICROBIOTA; SYMBIOSIS;

EID: 84920072880     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-014-0451-7     Document Type: Review

References (77)

1. Mariathasan S, Monack DM (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7(1):31–40. doi:10.1038/nri1997
2. Martinon F et al (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10(2):417–426
3. Henao-Mejia J et al (2014) Inflammasomes and metabolic disease. Annu Rev Physiol 76:57–78. doi:10.1146/annurev-physiol-021113-170324
4. Martinon F et al (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265. doi:10.1146/annurev.immunol.021908.132715
5. Thaiss CA et al (2014) The interplay between the innate immune system and the microbiota. Curr Opin Immunol 26:41–48. doi:10.1016/j.coi.2013.10.016
6. Munoz-Planillo R et al (2013) K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38(6):1142–1153. doi:10.1016/j.immuni.2013.05.016
7. Zambetti LP, Mortellaro A (2014) NLRPs, microbiota, and gut homeostasis: unravelling the connection. J Pathol. doi:10.1002/path.4357
8. Gagliani N et al (2014) Inflammasomes and intestinal homeostasis: regulating and connecting infection, inflammation and the microbiota. Int Immunol. doi:10.1093/intimm/dxu066
9. Zaki MH et al (2010) The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32(3):379–391. doi:10.1016/j.immuni.2010.03.003
10. Allen IC et al (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207(5):1045–1056. doi:10.1084/jem.20100050
11. Hirota SA et al (2011) NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm Bowel Dis 17(6):1359–1372. doi:10.1002/ibd.21478
12. Bauer C et al (2010) Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 59(9):1192–1199. doi:10.1136/gut.2009.197822
13. Bauer C et al (2012) Protective and aggravating effects of Nlrp3 inflammasome activation in IBD models: influence of genetic and environmental factors. Dig Dis 30(Suppl 1):82–90. doi:10.1159/000341681
14. Schoultz I et al (2009) Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn’s disease in Swedish men. Am J Gastroenterol 104(5):1180–1188. doi:10.1038/ajg.2009.29
15. Villani AC et al (2009) Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet 41(1):71–76. doi:10.1038/ng.285
16. Lewis GJ et al (2011) Genetic association between NLRP3 variants and Crohn’s disease does not replicate in a large UK panel. Inflamm Bowel Dis 17(6):1387–1391. doi:10.1002/ibd.21499
17. Mankan AK et al (2012) The NLRP3/ASC/Caspase-1 axis regulates IL-1beta processing in neutrophils. Eur J Immunol 42(3):710–715. doi:10.1002/eji.201141921
18. Guarda G et al (2011) Differential expression of NLRP3 among hematopoietic cells. J Immunol 186(4):2529–2534. doi:10.4049/jimmunol.1002720
19. Song-Zhao GX et al (2014) Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen. Mucosal Immunol 7(4):763–774. doi:10.1038/mi.2013.94
20. Elinav E et al (2013) Integrative inflammasome activity in the regulation of intestinal mucosal immune responses. Mucosal Immunol 6(1):4–13. doi:10.1038/mi.2012.115
21. Siegmund B (2010) Interleukin-18 in intestinal inflammation: friend and foe? Immunity 32(3):300–302. doi:10.1016/j.immuni.2010.03.010
22. Coccia M et al (2012) IL-1beta mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells. J Exp Med 209(9):1595–1609. doi:10.1084/jem.20111453
23. Zhang J et al (2014) Inflammasome activation has an important role in the development of spontaneous colitis. Mucosal Immunol 7(5):1139–1150. doi:10.1038/mi.2014.1
24. Thaiss CA, Elinav E (2014) Exploring new horizons in microbiome research. Cell Host Microbe 15(6):662–667. doi:10.1016/j.chom.2014.05.016
25. Grenier JM et al (2002) Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1. FEBS Lett 530(1–3):73–78
26. Elinav E et al (2011) NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145(5):745–757. doi:10.1016/j.cell.2011.04.022
27. Anand PK et al (2012) NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488(7411):389–393. doi:10.1038/nature11250
28. Normand S et al (2011) Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. Proc Natl Acad Sci U S A 108(23):9601–9606. doi:10.1073/pnas.1100981108
29. Chen GY et al (2011) A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J Immunol 186(12):7187–7194. doi:10.4049/jimmunol.1100412
30. Hu B et al (2013) Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci U S A 110(24):9862–9867. doi:10.1073/pnas.1307575110
31. Elinav E et al (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13(11):759–771. doi:10.1038/nrc3611
32. Mehal WZ (2013) The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol 10(11):637–644. doi:10.1038/nrgastro.2013.146
33. Sommer F, Backhed F (2013) The gut microbiota—masters of host development and physiology. Nat Rev Microbiol 11(4):227–238. doi:10.1038/nrmicro2974
34. Balmer ML et al (2014) The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med 6(237):237ra266. doi:10.1126/scitranslmed.3008618
35. Henao-Mejia J et al (2013) Role of the intestinal microbiome in liver disease. J Autoimmun 46:66–73. doi:10.1016/j.jaut.2013.07.001
36. Henao-Mejia J et al (2012) Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179–185. doi:10.1038/nature10809
37. Henao-Mejia J et al (2013) The intestinal microbiota in chronic liver disease. Adv Immunol 117:73–97. doi:10.1016/B978-0-12-410524-9.00003-7
38. Wlodarska M et al (2014) NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156(5):1045–1059. doi:10.1016/j.cell.2014.01.026
39. Patel KK et al (2013) Autophagy proteins control goblet cell function by potentiating reactive oxygen species production. EMBO J 32(24):3130–3144. doi:10.1038/emboj.2013.233
40. Wang L et al (2002) PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing. J Biol Chem 277(33):29874–29880. doi:10.1074/jbc.M203915200
41. Lich JD, Ting JP (2007) Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions. Microbes Infect / Institut Pasteur 9(5):672–676. doi:10.1016/j.micinf.2007.01.018
42. Allen IC et al (2012) NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-kappaB signaling. Immunity 36(5):742–754. doi:10.1016/j.immuni.2012.03.012
43. Williams KL et al (2005) The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals. J Biol Chem 280(48):39914–39924. doi:10.1074/jbc.M502820200
44. Ye Z et al (2008) ATP binding by monarch-1/NLRP12 is critical for its inhibitory function. Mol Cell Biol 28(5):1841–1850. doi:10.1128/MCB.01468-07
45. Arthur JC et al (2010) Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity. J Immunol 185(8):4515–4519. doi:10.4049/jimmunol.1002227
46. Allen IC et al (2013) Characterization of NLRP12 during the in vivo host immune response to Klebsiella pneumoniae and Mycobacterium tuberculosis. PLoS One 8(4):e60842. doi:10.1371/journal.pone.0060842
47. Vladimer GI et al (2012) The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37(1):96–107. doi:10.1016/j.immuni.2012.07.006
48. Zaki MH et al (2014) Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci U S A 111(1):385–390. doi:10.1073/pnas.1317643111
49. Ataide MA et al (2014) Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection. PLoS Pathog 10(1):e1003885. doi:10.1371/journal.ppat.1003885
50. Zaki MH et al (2011) The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell 20(5):649–660. doi:10.1016/j.ccr.2011.10.022
51. Franchi L et al (2006) Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nat Immunol 7(6):576–582. doi:10.1038/ni1346
52. Miao EA et al (2006) Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol 7(6):569–575. doi:10.1038/ni1344
53. Mariathasan S et al (2004) Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430(6996):213–218. doi:10.1038/nature02664
54. Kupz A et al (2014) In vivo IFN-gamma secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes. PLoS One 9(5):e97418. doi:10.1371/journal.pone.0097418
55. Franchi L et al (2012) NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 13(5):449–456. doi:10.1038/ni.2263
56. Franchi L et al (2007) Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation. Eur J Immunol 37(11):3030–3039. doi:10.1002/eji.200737532
57. Sutterwala FS et al (2007) Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J Exp Med 204(13):3235–3245. doi:10.1084/jem.20071239
58. Miao EA et al (2008) Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proc Natl Acad Sci U S A 105(7):2562–2567. doi:10.1073/pnas.0712183105
59. Ren T et al (2006) Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog 2(3):e18. doi:10.1371/journal.ppat.0020018
60. Sun YH et al (2007) Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium. J Biol Chem 282(47):33897–33901. doi:10.1074/jbc.C700181200
61. Suzuki T et al (2007) Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog 3(8):e111. doi:10.1371/journal.ppat.0030111
62. Zamboni DS et al (2006) The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunol 7(3):318–325. doi:10.1038/ni1305
63. Amer A et al (2006) Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J Biol Chem 281(46):35217–35223. doi:10.1074/jbc.M604933200
64. Man SM et al (2014) Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci U S A 111(20):7403–7408. doi:10.1073/pnas.1402911111
65. Lightfield KL et al (2008) Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat Immunol 9(10):1171–1178. doi:10.1038/ni.1646
66. Kofoed EM, Vance RE (2011) Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature 477(7366):592–595. doi:10.1038/nature10394
67. Zhao Y et al (2011) The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477(7366):596–600. doi:10.1038/nature10510
68. Manicassamy S et al (2010) Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329(5993):849–853. doi:10.1126/science.1188510
69. Smythies LE et al (2005) Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 115(1):66–75. doi:10.1172/JCI19229
70. Franchi L et al (2009) Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 183(2):792–796. doi:10.4049/jimmunol.0900173
71. Lotz M et al (2006) Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med 203(4):973–984. doi:10.1084/jem.20050625
72. Smith PD et al (2001) Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J Immunol 167(5):2651–2656
73. Meunier E et al (2014) Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature 509(7500):366–370. doi:10.1038/nature13157
74. Kayagaki N et al (2011) Non-canonical inflammasome activation targets caspase-11. Nature 479(7371):117–121. doi:10.1038/nature10558
75. Broz P et al (2012) Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature 490(7419):288–291. doi:10.1038/nature11419
76. Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasomes. Cell 157(5):1013–1022. doi:10.1016/j.cell.2014.04.007
77. Demon D et al (2014) Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulfate-induced colitis. Mucosal Immunol. doi:10.1038/mi.2014.36