Aggregatibacter actinomycetemcomitans cytolethal distending toxin activates the NLRP3 inflammasome in human macrophages, leading to the release of proinflammatory cytokines

Infection and Immunity

Volumn 83, Issue 4, 2015, Pages 1487-1496

  Shenker, Bruce J ^a   Ojcius, David M ^b   Walker, Lisa P ^a   Zekavat, Ali ^a   Scuron, Monika Damek ^a   Boesze Battaglia, Kathleen ^a  

^a UNIVERSITY OF PENNSYLVANIA SCHOOL OF DENTAL MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CRYOPYRIN; CYTOLETHAL DISTENDING TOXIN; INFLAMMASOME; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; PURINERGIC P2X7 RECEPTOR; REACTIVE OXYGEN METABOLITE; SHORT HAIRPIN RNA; BACTERIAL TOXIN; CARRIER PROTEIN; CYTOKINE; CYTOLETHAL DISTENDING TOXIN, ACTINOBACILLUS ACTINOMYCETEMCOMITANS; IL1B PROTEIN, HUMAN; IL6 PROTEIN, HUMAN; INTERLEUKIN 6; NLRP3 PROTEIN, HUMAN; PHOSPHATASE; PHOSPHATIDYLINOSITOL-3,4,5-TRISPHOSPHATE 5-PHOSPHATASE; POTASSIUM; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR;

AGGREGATIBACTER ACTINOMYCETEMCOMITANS; ARTICLE; BACTERIAL VIRULENCE; CELL ACTIVATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOKINE RESPONSE; CYTOTOXICITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME RELEASE; HUMAN; HUMAN CELL; MACROPHAGE; NONHUMAN; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTEIN EXPRESSION; WESTERN BLOTTING; GENETICS; IMMUNOLOGY; INFLAMMATION; METABOLISM; MICROBIOLOGY; RNA INTERFERENCE; SECRETION (PROCESS); TUMOR CELL LINE;

ADENOSINE TRIPHOSPHATE; BACTERIAL TOXINS; CARRIER PROTEINS; CASPASE 1; CELL LINE, TUMOR; CYTOKINES; ENZYME ACTIVATION; HUMANS; INFLAMMASOMES; INFLAMMATION; INTERLEUKIN-18; INTERLEUKIN-1BETA; INTERLEUKIN-6; MACROPHAGES; PHOSPHORIC MONOESTER HYDROLASES; POTASSIUM; REACTIVE OXYGEN SPECIES; RECEPTORS, PURINERGIC P2X7; RNA INTERFERENCE; RNA, SMALL INTERFERING; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84925372815     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.03132-14     Document Type: Article

References (51)

1. Comayras C, Tasca C, Peres SY, Ducommun B, Oswald E, De Rycke J. 1997. Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2/M transition by preventing cdc2 protein kinase dephosphorylation and activation. Infect Immun 65:5088-5095.
2. Okuda J, Fukumoto M, Takeda Y, Nishibuchi M. 1997. Examination of diarrheagenicity of cytolethal distending toxin: suckling mouse response to the products of the cdtABC genes of Shigella dysenteriae. Infect Immun 65:428-433.
3. Okuda J, Kurazono H, Takeda Y. 1995. Distribution of the cytolethal distending toxin A gene (cdtA) among species of Shigella and Vibrio, and cloning and sequencing of the cdt gene from Shigella dysenteriae. Microb Pathog 18:167-172.
4. Scott DA, Kaper JB. 1994. Cloning and sequencing of the genes encoding Escherichia coli cytolethal distending toxin. Infect Immun 62:244-251.
5. Pickett CL, Cottle DL, Pesci EC, Bikah G. 1994. Cloning, sequencing, and expression of the Escherichia coli cytolethal distending toxin genes. Infect Immun 62:1046-1051.
6. Mayer MP, Bueno LC, Hansen EJ, DiRienzo JM. 1999. Identification of a cytolethal distending toxin gene locus and features of a virulenceassociated region in Actinobacillus actinomycetemcomitans. Infect Immun 67:1227-1237.
7. Pickett CL, Whitehouse CA. 1999. The cytolethal distending toxin family. Trends Microbiol 7:292-297. http://dx.doi.org/10.1016/S0966-842X(99)01537-1.
8. Shenker BJ, McKay TL, Datar S, Miller M, Chowhan R, Demuth DR. 1999. Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the family of cytolethal distending toxins capable of causing a G2 arrest in human T cells. J Immunol 162:4773-4780.
9. Shenker BJ, Hoffmaster RH, McKay TL, Demuth DR. 2000. Expression of the cytolethal distending toxin (Cdt) operon in Actinobacillus actinomycetemcomitans: evidence that the CdtB protein is responsible for G2 arrest of the cell cycle in human T-cells. J Immunol 165:2612-2618. http://dx.doi.org/10.4049/jimmunol.165.5.2612.
10. Shenker BJ, Hoffmaster RH, Zekavat A, Yamguchi N, Lally ET, Demuth DR. 2001. Induction of apoptosis in human T cells by Actinobacillus actinomycetemcomitans cytolethal distending toxin is a consequence of G2 arrest of the cell cycle. J Immunol 167:435-441. http://dx.doi.org/10.4049/jimmunol.167.1.435.
11. De Rycke J, Oswald E. 2001. Cytolethal distending toxin (CDT): a bacterial weapon to control host cell proliferaton? FEMS Microbiol Lett 203: 141-148. http://dx.doi.org/10.1111/j.1574-6968.2001.tb10832.x.
12. Thelestam M, Frisan T. 2004. Cytolethal distending toxins. Rev Physiol Biochem Pharmacol 152:111-133. http://dx.doi.org/10.1007/s10254-004-0030-8.
13. Nesic D, Hsu Y, Stebbins CE. 2004. Assembly and function of a bacterial genotoxin. Nature 429:429-433. http://dx.doi.org/10.1038/nature02532.
14. Elwell CA, Chao K, Patel K, Dreyfus LA. 2001. Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest. Infect Immun 69: 3418-3422. http://dx.doi.org/10.1128/IAI.69.5.3418-3422.2001.
15. Lara-Tejero M, Galan JE. 2001. CdtA, CdtB, and CdtC form a tripartite complex that is required for cytolethal distending toxin activity. Infect Immun 69:4358-4365. http://dx.doi.org/10.1128/IAI.69.7.4358-4365.2001.
16. Boesze-Battaglia K, Besack D, McKay TL, Zekavat A, Otis L, Jordan-Sciutto K, Shenker BJ. 2006. Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin. Cell Microbiol 8:823-836. http://dx.doi.org/10.1111/j.1462-5822.2005.00669.x.
17. Boesze-Battaglia K, Brown A, Walker L, Besack D, Zekavat A, Wrenn S, Krummenacher C, Shenker BJ. 2009. Cytolethal distending toxininduced cell cycle arrest of lymphocytes is dependent upon recognition and binding to cholesterol. J Biol Chem 284:10650-10658. http://dx.doi.org/10.1074/jbc.M809094200.
18. Shenker BJ, Dlakic M, Walker L, Besack D, Jaffe E, Labelle E, Boesze-Battaglia K. 2007. A novel mode of action for a microbial-derived immunotoxin: the cytolethal distending toxin subunit B exhibits phosphatidylinositol 3,4,5-triphosphate phosphatase activity. J Immunol 178:5099-5108. http://dx.doi.org/10.4049/jimmunol.178.8.5099.
19. Shenker B, Walker L, Zekavat A, Dlakic M, Boesze-Battaglia K. 2014. Blockade of the PI-3K signaling pathway by the Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces macrophages to synthesize and secrete pro-inflammatory cytokines. Cell Microbiol 16:1391-1404. http://dx.doi.org/10.1111/cmi.12299.
20. Antoniv T, Ivashkiv L. 2011. Interleukin-10-induced gene expression and suppressive function are selectively modulated by the PI3K-Akt-GSK3 pathway. Immunology 132:567-577. http://dx.doi.org/10.1111/j.1365-2567.2010.03402.x.
21. Arbibe L, Mira J-P, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Knaus U. 2000. Toll-like receptor 2-mediated NF-κB activation requires a Rac1-dependent pathway. Nat Immunol 1:533-540. http://dx.doi.org/10.1038/82797.
22. Brown J, Wang H, Hajishengallis H, Martin M. 2011. TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J Dent Res 90:417-427. http://dx.doi.org/10.1177/0022034510381264.
23. Guha M, Mackman N. 2002. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 277:32124-32132. http://dx.doi.org/10.1074/jbc.M203298200.
24. Hazeki K, Nigorikawa K, Hazeki O. 2007. Role of phosphoinositide 3-kinase in innate immunity. Biol Pharm Bull 30:1617-1623. http://dx.doi.org/10.1248/bpb.30.1617.
25. Molnarfi N, Gruaz L, Dayer J, Burger D. 2007. Opposite regulation of IL-1β and secreted IL-1 receptor antagonist production by phophatidylinositide-kinases in human monocytes activated by lipopolysaccharides or contact with T cells. J Immunol 178:446-454. http://dx.doi.org/10.4049/jimmunol.178.1.446.
26. Ohtani M, Nagai S, Kondo S, Mizuno S, Nakamura K, Tanabe M, Takeuchi T, Matsuda S, Koyasu S. 2008. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharideinduced interleukin-12 production in dendritic cells. Blood 112:635-643. http://dx.doi.org/10.1182/blood-2008-02-137430.
27. Wang H, Garcia C, Rehani K, Cekic C, Alard P, Kinane D, Mitchell T, Martin M. 2008. IFN-β production by TLR4-stimulated innate immune cells is negatively regulated by GSK3-β. J Immunol 181:6797-6802. http://dx.doi.org/10.4049/jimmunol.181.10.6797.
28. Weichhart T, Costantino G, Poglitsch M, Rosner M, Zeyda M, Stuhlmeier K, Kolbe T, Stulnig T, Horl W, Hengstschlager M, Muller M. 2008. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29:565-577. http://dx.doi.org/10.1016/j.immuni.2008.08.012.
29. Said-Sadier N, Padilla E, Langsley G, Ojcius D. 2010. Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5:e10008. http://dx.doi.org/10.1371/journal.pone.0010008.
30. Abdul-Sater A, Said-Sadier N, Padilla E, Ojcius D. 2010. Chlamydial infection of monocytes stimulates IL-1β secretion through activation of the NLRP3 inflammasome. Microbes Infect 12:652-661. http://dx.doi.org/10.1016/j.micinf.2010.04.008.
31. Chen C, Tsai S, Hu S, Wu T, Huang T, Said-Sadier N, Ojcius D, Lai H. 2012. Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection. PLoS One 7:e36292. http://dx.doi.org/10.1371/journal.pone.0036292.
32. Zhu Y, Jiang J, Said-Sadier N, Boxx G, Champion C, Tetlow A, Kickhoefer V, Rome L, Ojcius D, Kelly K. 2015. Activation of the NLRP3 inflammasome by vault nanoparticles expressing a chlamydial epitope. Vaccine 33:298-306. http://dx.doi.org/10.1016/j.vaccine.2014.11.028.
33. Shenker BJ, Besack D, McKay TL, Pankoski L, Zekavat A, Demuth DR. 2004. Actinobacillus actinomycetemcomitans cytolethal distending toxin (Cdt). Evidence that the holotoxin is composed of three subunits: CdtA, CdtB, and CdtC. J Immunol 172:410-417. http://dx.doi.org/10.4049/jimmunol.172.1.410.
34. Shenker B, Boesze-Battaglia K, Zekavat A, Walker L, Besack D, Ali H. 2010. Inhibition of mast cell degranulaton by a chimeric toxin containing a novel phsphatidylinositol-3,4,5-triphosphate phosphatase. Mol Immunol 48:203-210. http://dx.doi.org/10.1016/j.molimm.2010.08.009.
35. Mariathasan S, Monack D. 2007. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7:31-40. http://dx.doi.org/10.1038/nri1997.
36. Pedra J, Cassel S, Sutterwala F. 2009. Sensing pathogens and danger signals by the inflammasome. Curr Opin Immunol 21:10-16. http://dx.doi.org/10.1016/j.coi.2009.01.006.
37. Huang T, Ojcius D, Young J, Wu Y, Ko Y, Wong T, Wu C, Lu C, Lai H. 2012. The anti-tumorigenic mushroom Agaricus blazei Murill enhances IL-1β production and activates the NLRP3 inflammasome in human macrophages. PLoS One 7:e41383. http://dx.doi.org/10.1371/journal.pone.0041383.
38. Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, J van der Meer JH, van de Veerdonk FL, Ferwerda G, Heinhuis B, Devesa I, Funk CJ, Mason RJ, Kullberg BJ, Rubartelli A, van der Meer JW, Dinarello CA. 2009. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 113:2324-2335. http://dx.doi.org/10.1182/blood-2008-03-146720.
39. Yilmaz O, Sater A, Yao L, Koutouzis T, Pettengill M, Ojcius D. 2010. ATP-dependent activation of an inflammasome in primary gingival epithelial cells infected by Porphyromonas gingivalis. Cell Microbiol 12:188-198. http://dx.doi.org/10.1111/j.1462-5822.2009.01390.x.
40. Bratel J, Haraldson T, Meding B, Yontchev E, Ohman S-C, Ottosson J-O. 1997. Potential side effects of dental amalgam restorations. (I) An oral and medical investigation. Eur J Oral Sci 105:234-243.
41. Broz P, von Moltke J, Jones JW, Vance RE, Monack DM. 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.
42. Franchi L, Munoz-Planillo R, Nunez G. 2012. Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13:325-332. http://dx.doi.org/10.1038/ni.2231.
43. Belibasakis G, Johansson A. 2012. Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes. Cytokine 59:124-130. http://dx.doi.org/10.1016/j.cyto.2012.03.016.
44. Barker B, Taxman D, Ting J. 2011. Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines. Curr Opin Immunol 23:591-597. http://dx.doi.org/10.1016/j.coi.2011.07.005.
45. Dubyak G. 2012. P2X7 receptor regulation of non-classical secretion from immune effector cells. Cell Microbiol 14:1697-1706. http://dx.doi.org/10.1111/cmi.12001.
46. Ciraci C, Janczy J, Sutterwala F, Cassel S. 2012. Control of innate and adaptive immunity by the inflammasome. Microbes Infect 14:1263-1270. http://dx.doi.org/10.1016/j.micinf.2012.07.007.
47. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228-232. http://dx.doi.org/10.1038/nature04515.
48. Andrukhov O, Ulm C, Reischl H, Nguyen P, Matejka M, Rausch-Fan X. 2011. Serum cytokine levels in periodontitis patients in relation to the bacterial load. J Periodontol 82:885-892. http://dx.doi.org/10.1902/jop.2010.100425.
49. de Brito Bezerra B, Andriankaja O, Kang J, Pacios S, Bae HJ, Li Y, Tslagbe V, Schreiner H, Fine DH, Graves DT. 2012. A. actinomycetemcomitans-induced periodontal disease promotes systemic and local responses in rat periodontium. J Clin Periodontol 39:333-341. http://dx.doi.org/10.1111/j.1600-051X.2011.01847.x.
50. Fredman G, Oh SF, Ayilavarapu S, Hasturk H, Serhan CN, Van Dyke TE. 2011. Impaired phagocytosis in localized aggressive periodontitis: rescue by resolvin E1. PLoS One 6:e24422. http://dx.doi.org/10.1371/journal.pone.0024422.
51. Hajishengallis G, Darveau R, Curtis M. 2012. The keystone-pathogen hypothesis. Nat Rev Microbiol 10:717-725. http://dx.doi.org/10.1038/nrmicro2873.