More than a pore: The cellular response to cholesterol-dependent cytolysins

Toxins

Volumn 5, Issue 4, 2013, Pages 618-636

  Cassidy, Sara K B ^a   O'Riordan, Mary X D ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

CDC; Cellular response; Cholesterol dependent cytolysins; Membrane repair; Pore formation; Signaling; Survival

Indexed keywords

CHOLESTEROL DEPENDENT CYTOLYSIN PROTEIN; PORE FORMING CYTOTOXIC PROTEIN; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; APOPTOSIS; CELL MEMBRANE TRANSPORT; CELL NUCLEUS; CELL ORGANELLE; CELL SURVIVAL; CHANNEL GATING; CYTOTOXICITY; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; GOLGI COMPLEX; HOST CELL; HOST PATHOGEN INTERACTION; HUMAN; INNATE IMMUNITY; LYSOSOME MEMBRANE; MEMBRANE BINDING; MITOCHONDRION; NONHUMAN; OLIGOMERIZATION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

EID: 84876195895     PISSN: 20726651     EISSN: None     Source Type: Journal    
DOI: 10.3390/toxins5040618     Document Type: Review

References (107)

1. Sierig, G.; Cywes, C.; Wessels, M.R.; Ashbaugh, C.D. Cytotoxic effects of streptolysin O and streptolysin S enhance the virulence of poorly encapsulated group A streptococci. Infect. Immun. 2003, 71, 446-455.
2. Magassa, N.A.G.; Chandrasekaran, S.; Caparon, M.G. Streptococcus pyogenes cytolysin-mediated translocation does not require pore formation by streptolysin O. EMBO Rep. 2010, 11, 400-405.
3. Portnoy, D.A.; Jacks, P.S.; Hinrichs, D.J. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J. Exp. Med. 1988, 167, 1459-1471.
4. Chu, J.; Thomas, L.M.; Watkins, S.C.; Franchi, L.; Núñez, G.; Salter, R.D. Cholesterol-dependent cytolysins induce rapid release of mature IL-1beta from murine macrophages in a NLRP3 inflammasome and cathepsin B-dependent manner. J. Leukoc. Biol. 2009, 86, 1227-1238.
5. Baba, H.; Kawamura, I.; Kohda, C.; Nomura, T.; Ito, Y.; Kimoto, T.; Watanabe, I.; Ichiyama, S.; Mitsuyama, M. Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity. Infect. Immun. 2002, 70, 107-113.
6. Walev, I.; Palmer, M.; Martin, E.; Jonas, D.; Weller, U.; Höhn-Bentz, H.; Husmann, M.; Bhakdi, S. Recovery of human fibroblasts from attack by the pore-forming alpha-toxin of Staphylococcus aureus. Microb. Pathog. 1994, 17, 187-201.
7. Jacobs, T.; Darji, A.; Frahm, N.; Rohde, M.; Wehland, J.; Chakraborty, T.; Weiss, S. Listeriolysin O: Cholesterol inhibits cytolysis but not binding to cellular membranes. Mol. Microbiol. 1998, 28, 1081-1089.
8. + efflux is necessary for histone H3 dephosphorylation by Listeria monocytogenes listeriolysin O and other pore forming toxins. Infect. Immun. 2011, 79, 2839-2846.
9. Jones, S.; Prieter, K.; Portnoy, D.A. Conversion of an extracellular cytolysin into a phagosome-specific lysin which supports the growth of an intracellaulr pathogen. Mol. Micro. 1996, 21, 1219-1225.
10. Dunstone, M.A.; Tweten, R.K. Packing a punch: the mechanism of pore formation by cholesterol dependent cytolysins and membrane attack complex/perforin-like proteins. Curr. Opin. Struct. Biol. 2012, 22, 342-349.
11. Kafsack, B.F.C.; Pena, J.D.O.; Coppens, I.; Ravindran, S.; Boothroyd, J.C.; Carruthers, V.B. Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 2009, 323, 530-533.
12. Sousa, M.V.; Richardson, M.; Fontes, W.; Morhy, L. Homology between the seed cytolysin enterolobin and bacterial aerolysins. J. Protein Chem. 1994, 13, 659-667.
13. Walev, I.; Bhakdi, S.C.; Hofmann, F.; Djonder, N.; Valeva, A.; Aktories, K.; Bhakdi, S. Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O. Proc. Natl. Acad. Sci. USA 2001, 98, 3185-3190.
14. Lopez, J.A.; Susanto, O.; Jenkins, M.R.; Lukoyanova, N.; Sutton, V.R.; Law, R.H.P.; Johnston, A.; Bird, C.H.; Bird, P.I.; Whisstock JC, et al. Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack. Blood 2013, doi:10.1182/blood-2012-07-446146.
15. Heuck, A.P.; Moe, P.C.; Johnson, B.B. The cholesterol-dependent cytolysin family of gram-positive bacterial toxins. Subcell. Biochem. 2010, 51, 551-577.
16. Rossjohn, J.; Feil, S.C.; McKinstry, W.J.; Tweten, R.K.; Parker, M.W. Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Cell 1997, 89, 685-692.
17. Polekhina, G.; Giddings, K.S.; Tweten, R.K.; Parker, M.W. Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin. Proc. Natl. Acad. Sci. USA 2005, 102, 600-605.
18. Bourdeau, R.W.; Malito, E.; Chenal, A.; Bishop, B.L.; Musch, M.W.; Villereal, M.L.; Chang, E.B.; Mosser, E.M.; Rest, R.F.; Tang, W.-J. Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis. J. Biol. Chem. 2009, 284, 14645-14656.
19. Xu, L.; Huang, B.; Du, H.; Zhang, X.C.; Xu, J.; Li, X.; Rao, Z. Crystal structure of cytotoxin protein suilysin from Streptococcus suis. Protein Cell 2010, 1, 96-105.
20. Hotze, E.M.; Tweten, R.K. Membrane assembly of the cholesterol-dependent cytolysin pore complex. Biochim. Biophys. Acta 2012, 1818, 1028-1038.
21. Soltani, C.E.; Hotze, E.M.; Johnson, A.E.; Tweten, R.K. Structural elements of the cholesterol-dependent cytolysins that are responsible for their cholesterol-sensitive membrane interactions. Proc. Natl. Acad. Sci. USA 2007, 104, 20226-20231.
22. Dowd, K.J.; Tweten, R.K. The cholesterol-dependent cytolysin signature motif: A critical element in the allosteric pathway that couples membrane binding to pore assembly. PLoS Pathog. 2012, 8, e1002787.
23. Giddings, K.S.; Zhao, J.; Sims, P.J.; Tweten, R.K. Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin. Nat. Struct. Mol. Biol. 2004, 11, 1173-1178.
24. Gelber, S.E.; Aguilar, J.L.; Lewis, K.L.T.; Ratner, A.J. Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J. Bacteriol. 2008, 190, 3896-3903.
25. Gekara, N.O.; Weiss, S. Lipid rafts clustering and signalling by listeriolysin O. Biochem. Soc. Trans. 2004, 32, 712-714.
26. Gekara, N.O.; Jacobs, T.; Chakraborty, T.; Weiss, S. The cholesterol-dependent cytolysin listeriolysin O aggregates rafts via oligomerization. Cell. Microbiol. 2005, 7, 1345-1356.
27. Nelson, L.D.; Chiantia, S.; London, E. Perfringolysin O association with ordered lipid domains: Implications for transmembrane protein raft affinity. Biophys. J. 2010, 99, 3255-3263.
28. Simons, K.; Toomre, D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 2000, 1, 31-39.
29. Zitzer, A.; Bittman, R.; Verbicky, C.A.; Erukulla, R.K.; Bhakdi, S.; Weis, S.; Valeva, A.; Palmer, M. Coupling of cholesterol and cone-shaped lipids in bilayers augments membrane permeabilization by the cholesterol-specific toxins streptolysin O and Vibrio cholerae cytolysin. J. Biol. Chem. 2001, 276, 14628-14633.
30. Kouzel, I.U.; Pohlentz, G.; Storck, W.; Radamm, L.; Hoffmann, P.; Bielaszewska, M.; Bauwens, A.; Cichon, C.; Schmidt, M.A.; Mormann, M.; Karch, H.; Müthing, J. Association of Shiga toxin glycosphingolipid receptors with membrane microdomains of toxin-sensitive lymphoid and myeloid cells. J. Lipid Res. 2013, 54, 692-710.
31. Tilley, S.J.; Orlova, E.V.; Gilbert, R.J.C.; Andrew, P.W.; Saibil, H.R. Structural basis of pore formation by the bacterial toxin pneumolysin. Cell 2005, 121, 247-256.
32. Ramachandran, R.; Heuck, A.P.; Tweten, R.K.; Johnson, A.E. Structural insights into the membrane-anchoring mechanism of a cholesterol-dependent cytolysin. Nat. Struct. Biol. 2002, 9, 823-827.
33. Tweten, R.K. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 2005, 73, 6199-6209.
34. Bhakdi, S.; Tranum-Jensen, J.; Sziegoleit, A. Mechanism of membrane damage by streptolysin-O. Infect. Immun. 1985, 47, 52-60.
35. Schuerch, D.W.; Wilson-Kubalek, E.M.; Tweten, R.K. Molecular basis of listeriolysin O pH dependence. Proc. Natl. Acad. Sci. USA 2005, 102, 12537-12542.
36. Czajkowsky, D.M.; Hotze, E.M.; Shao, Z.; Tweten, R.K. Vertical collapse of a cytolysin prepore moves its transmembrane beta-hairpins to the membrane. EMBO J. 2004, 23, 3206-3215.
37. Shaughnessy, L.M.; Hoppe, A.D.; Christensen, K.A.; Swanson, J.A. Membrane perforations inhibit lysosome fusion by altering pH and calcium in Listeria monocytogenes vacuoles. Cell. Microbiol. 2006, 8, 781-792.
38. Palmer, M.; Harris, R.; Freytag, C.; Kehoe, M.; Tranum-Jensen, J.; Bhakdi, S. Assembly mechanism of the oligomeric streptolysin O pore: The early membrane lesion is lined by a free edge of the lipid membrane and is extended gradually during oligomerization. EMBO J. 1998, 17, 1598-1605.
39. Gilbert, R.J.C.; Mikelj, M.; Dalla Serra, M.; Froelich, C.J.; Anderluh, G. Effects of MACPF/CDC proteins on lipid membranes. Cell. Mol. Life Sci. 2012, doi:10.1007/s00018-012-1153-8.
40. Seong, S.-Y.; Matzinger, P. Hydrophobicity: An ancient damage-associated molecular pattern that initiates innate immune responses. Nat. Rev. Immunol. 2004, 4, 469-478.
41. Bhakdi, S.; Weller, U.; Walev, I.; Martin, E.; Jonas, D.; Palmer, M. A guide to the use of pore-forming toxins for controlled permeabilization of cell membranes. Med. Microbiol. Immunol. 1993, 182, 167-175.
42. Gonzalez, M.R.; Bischofberger, M.; Frêche, B.; Ho, S.; Parton, R.G.; van der Goot, F.G. Pore-forming toxins induce multiple cellular responses promoting survival. Cell. Microbiol. 2011, 13, 1026-1043.
43. Rao, S.K.; Huynh, C.; Proux-Gillardeaux, V.; Galli, T.; Andrews, N.W. Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J. Biol. Chem. 2004, 279, 20471-20479.
44. 2+-regulated exocytic vesicles in fibroblasts and epithelial cells. J. Cell Biol. 1997, 137, 93-104.
45. 2+-dependent endocytosis. J. Cell Biol. 2008, 180, 905-914.
46. Tam, C.; Idone, V.; Devlin, C.; Fernandes, M.C.; Flannery, A.; He, X.; Schuchman, E.; Tabas, I.; Andrews, N.W. Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. J. Cell Biol. 2010, 189, 1027-1038.
47. Truman, J.-P.; Al Gadban, M.M.; Smith, K.J.; Hammad, S.M. Acid sphingomyelinase in macrophage biology. Cell. Mol. Life Sci. 2011, 68, 3293-3305.
48. Grassme, H.; Jendrossek, V.; Bock, J.; Riehle, A.; Gulbins, E. Ceramide-rich membrane rafts mediate CD40 clustering. J. Immunol. 2002, 168, 298-307.
49. Corrotte, M.; Fernandes, M.C.; Tam, C.; Andrews, N.W. Toxin pores endocytosed during plasma membrane repair traffic into the lumen of MVBs for degradation. Traffic 2012, 13, 483-494.
50. Reddy, A.; Caler, E.V.; Andrews, N.W. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Cell 2001, 106, 157-169.
51. Lesieur, C.; Frutiger, S.; Hughes, G.; Kellner, R.; Pattus, F.; van der Goot, F.G. Increased stability upon heptamerization of the pore-forming toxin aerolysin. J. Biol. Chem. 1999, 274, 36722-36728.
52. Kerr, J.F.; Wyllie, A.H.; Currie, A.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 1972, 26, 239-257.
53. Charras, G.; Paluch, E. Blebs lead the way: How to migrate without lamellipodia. Nat. Rev. Mol. Cell Biol. 2008, 9, 730-736.
54. Babiychuk, E.B.; Monastyrskaya, K.; Potez, S.; Draeger, A. Blebbing confers resistance against cell lysis. Cell Death Differ. 2011, 18, 80-89.
55. Keyel, P.A.; Loultcheva, L.; Roth, R.; Salter, R.D.; Watkins, S.C.; Yokoyama, W.M.; Heuser, J.E. Streptolysin O clearance through sequestration into blebs that bud passively from the plasma membrane. J. Cell Sci. 2011, 124, 2414-2423.
56. Cassidy, S.K.B.; Hagar, J.A.; Kanneganti, T.-D.; Franchi, L.; Núñez, G.; O'Riordan, M.X.D. Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response. PLoS Pathog. 2012, 8, e1002628.
57. Sebbagh, M.; Renvoizé, C.; Hamelin, J.; Riché, N.; Bertoglio, J.; Bréard, J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat. Cell Biol. 2001, 3, 346-352.
58. Coleman, M.L.; Sahai, E.A.; Yeo, M.; Bosch, M.; Dewar, A.; Olson, M.F. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 2001, 3, 339-345.
59. Pillich, H.; Loose, M.; Zimmer, K.-P.; Chakraborty, T. Activation of the unfolded protein response by Listeria monocytogenes. Cell. Microbiol. 2012, 14, 949-964.
60. Todd, D.J.; Lee, A.-H.; Glimcher, L.H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat. Rev. Immunol. 2008, 8, 663-674.
61. Bischof, L.J.; Kao, C.-Y.; Los, F.C.O.; Gonzalez, M.R.; Shen, Z.; Briggs, S.P.; van der Goot, F.G.; Aroian, R.V. Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog. 2008, 4, e1000176.
62. Høyer-Hansen, M.; Jäättelä, M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 2007, 14, 1576-1582.
63. Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007, 8, 519-529.
64. Schröder, M.; Kaufman, R.J. The mammalian unfolded protein response. Annu. Rev. Biochem. 2005, 74, 739-789.
65. Flanagan, J.J.; Tweten, R.K.; Johnson, A.E.; Heuck, A.P. Cholesterol exposure at the membrane surface is necessary and sufficient to trigger perfringolysin O binding. Biochemistry 2009, 48, 3977-3987.
66. Van Meer, G.; Voelker, D.R.; Feigenson, G.W. Membrane lipids: Where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008, 9, 112-124.
67. 2+ signalling by listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes. Cell. Microbiol. 2007, 9, 2008-2021.
68. Kobayashi, T.; Pimplikar, S.W.; Parton, R.G.; Bhakdi, S.; Simons, K. Sphingolipid transport from the trans-Golgi network to the apical surface in permeabilized MDCK cells. FEBS Lett. 1992, 300, 227-231.
69. Bankaitis, V.A.; Garcia-Mata, R.; Mousley, C.J. Golgi membrane dynamics and lipid metabolism. Curr. Biol. 2012, 22, R414-R424.
70. Divangahi, M.; Chen, M.; Gan, H.; Desjardins, D.; Hickman, T.T.; Lee, D.M.; Fortune, S.; Behar, S.M.; Remold, H.G. Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat. Immunol. 2009, 10, 899-906.
71. Goldmann, O.; Sastalla, I.; Wos-Oxley, M.; Rohde, M.; Medina, E. Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway. Cell. Microbiol. 2009, 11, 138-155.
72. Braun, J.S.; Hoffmann, O.; Schickhaus, M.; Freyer, D.; Dagand, E.; Bermpohl, D.; Mitchell, T.J.; Bechmann, I.; Weber, J.R. Pneumolysin causes neuronal cell death through mitochondrial damage. Infect Immun. 2007, 75, 4245-4254.
73. Stavru, F.; Bouillaud, F.; Sartori, A.; Ricquier, D.; Cossart, P. Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc. Natl. Acad. Sci. USA 2011, 108, 3612-3617.
74. Hamon, M.A.; Batsché, E.; Régnault, B.; Tham, T.N.; Seveau, S.; Muchardt, C.; Cossart, P. Histone modifications induced by a family of bacterial toxins. Proc. Natl. Acad. Sci. USA 2007, 104, 13467-13472.
75. Kayal, S.; Lilienbaum, A.; Poyart, C.; Memet, S.; Israel, A.; Berche, P. Listeriolysin O-dependent activation of endothelial cells during infection with Listeria monocytogenes: Activation of NF-kappa B and upregulation of adhesion molecules and chemokines. Mol. Microbiol. 1999, 31, 1709-1722.
76. Tang, P.; Rosenshine, I.; Cossart, P.; Finlay, B.B. Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells. Infect. Immun. 1996, 64, 2359-2361.
77. Samba-Louaka, A.; Stavru, F.; Cossart, P. Role for telomerase in Listeria monocytogenes infection. Infect. Immun. 2012, 80, 4257-4263.
78. Schnupf, P.; Portnoy, D.A. Listeriolysin O: A phagosome-specific lysin. Microbes Infect. 2007, 9, 1176-1187.
79. Shaughnessy, L.M.; Lipp, P.; Lee, K.-D.; Swanson, J.A. Localization of protein kinase C epsilon to macrophage vacuoles perforated by Listeria monocytogenes cytolysin. Cell. Microbiol. 2007, 9, 1695-1704.
80. Henry, R.; Shaughnessy, L.; Loessner, M.J.; Alberti-Segui, C.; Higgins, D.E.; Swanson, J.A. Cytolysin-dependent delay of vacuole maturation in macrophages infected with Listeria monocytogenes. Cell. Microbiol. 2006, 8, 107-119.
81. Marquis, H.; Goldfine, H.; Portnoy, D.A. Proteolytic pathways of activation and degradation of a bacterial phospholipase C during intracellular infection by Listeria monocytogenes. J. Cell Biol. 1997, 137, 1381-1392.
82. Wadsworth, S.J.; Goldfine, H. Mobilization of protein kinase C in macrophages induced by Listeria monocytogenes affects its internalization and escape from the phagosome. Infect. Immun. 2002, 70, 4650-4660.
83. Birmingham, C.L.; Canadien, V.; Gouin, E.; Troy, E.B.; Yoshimori, T.; Cossart, P.; Higgins, D.E.; Brumell, J.H. Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy 2007, 3, 442-451.
84. Meyer-Morse, N.; Robbins, J.R.; Rae, C.S.; Mochegova, S.N.; Swanson, M.S.; Zhao, Z.; Virgin, H.W.; Portnoy, D. Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. PLoS One 2010, 5, e8610.
85. Logsdon, L.K.; Håkansson, A.P.; Cortés, G.; Wessels, M.R. Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. MBio 2011, 2, e00332-10.
86. Sakurai, A.; Maruyama, F.; Funao, J.; Nozawa, T.; Aikawa, C.; Okahashi, N.; Shintani, S.; Hamada, S.; Ooshima, T.; Nakagawa, I. Specific behavior of intracellular Streptococcus pyogenes that has undergone autophagic degradation is associated with bacterial streptolysin O and host small G proteins Rab5 and Rab7. J. Biol. Chem. 2010, 285, 22666-22675.
87. Thiery, J.; Keefe, D.; Boulant, S.; Boucrot, E.; Walch, M.; Martinvalet, D.; Goping, I.S.; Bleackley, R.C.; Kirchhausen, T.; Lieberman, J. Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells. Nat. Immunol.2011, 12, 770-777.
88. Davis, M.J.; Swanson, J.A. Technical advance: Caspase-1 activation and IL-1β release correlate with the degree of lysosome damage, as illustrated by a novel imaging method to quantify phagolysosome damage. J. Leukoc. Biol. 2010, 88, 813-822.
89. Hornung, V.; Bauernfeind, F.; Halle, A.; Samstad, E.O.; Kono, H.; Rock, K.L.; Fitzgerald, K.A.; Latz, E. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 2008, 9, 847-856.
90. Dong, C.; Davis, R.J.; Flavell, R.A. MAP kinases in the immune response. Annu. Rev. Immunol. 2002,20, 55-72.
91. Dogan, S.; Zhang, Q.; Pridmore, A.C.; Mitchell, T.J.; Finn, A.; Murdoch, C. Pneumolysin-induced CXCL8 production by nasopharyngeal epithelial cells is dependent on calcium flux and MAPK activation by Toll-like receptor 4. Microbes Infect. 2011, 13, 65-75.
92. Nilsson, M.; Sørensen, O.E.; Mörgelin, M.; Weineisen, M.; Sjöbring, U.; Herwald, H. Activation of human polymorphonuclear neutrophils by streptolysin O from Streptococcus pyogenes leads to the release of proinflammatory mediators. Thromb. Haemost. 2006, 95, 982-990.
93. Bebien, M.; Hensler, M.E.; Davanture, S.; Hsu, L.-C.; Karin, M.; Park, J.M.; Alexopoulou, L.; Liu, G.Y.; Nizet, V.; Lawrence, T. The pore-forming toxin β hemolysin/cytolysin triggers p38 MAPK-dependent IL-10 production in macrophages and inhibits innate immunity. PLoS Pathog. 2012,8, e1002812.
94. Hackett, S.P.; Stevens, D.L. Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O. J. Infect. Dis. 1992, 165, 879-885.
95. Houldsworth, S.; Andrew, P.W.; Mitchell, T.J. Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin-1 beta by human mononuclear phagocytes. Infect. Immun. 1994, 62, 1501-1503.
96. Malley, R.; Henneke, P.; Morse, S.C.; Cieslewicz, M.J.; Lipsitch, M.; Thompson, C.M.; Kurt-Jones, E.; Paton, J.C.; Wessels, M.R.; Golenbock, D.T. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc. Natl. Acad. Sci. USA 2003, 100, 1966-1971.
97. Park, J.M.; Ng, V.H.; Maeda, S.; Rest, R.F.; Karin, M. Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists. J. Exp. Med. 2004, 200, 1647-1655.
98. Zhang, H.; Tay, P.N.; Cao, W.; Li, W.; Lu, J. Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling. FEBS Lett. 2002, 532, 171-176.
99. Harder, J.; Franchi, L.; Muñoz-Planillo, R.; Park, J.-H.; Reimer, T.; Núñez, G. Activation of the Nlrp3 inflammasome by Streptococcus pyogenes requires streptolysin O and NF-kappa B activation but proceeds independently of TLR signaling and P2X7 receptor. J. Immunol. 2009, 183, 5823-5829.
100. Pétrilli, V.; Papin, S.; Dostert, C.; Mayor, A.; Martinon, F.; Tschopp, J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007, 14, 1583-1589.
101. Keyel, P.A.; Heid, M.E.; Salter, R.D. Macrophage responses to bacterial toxins: A balance between activation and suppression. Immunol. Res. 2011, 50, 118-123.
102. Carrero, J.A.; Vivanco-Cid, H.; Unanue, E.R. Listeriolysin O is strongly immunogenic independently of its cytotoxic activity. PLoS One 2012, 7, e32310.
103. Wallecha, A.; Wood, L.; Pan, Z.-K.; Maciag, P.C.; Shahabi, V.; Paterson, Y. Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular pattern-like properties independent of its hemolytic ability. Clin. Vaccine Immunol. 2013, 20, 77-84.
104. Harty, J.T.; Schreiber, R.D.; Bevan, M.J. CD8 T cells can protect against an intracellular bacterium in an interferon gamma-independent fashion. Proc. Natl. Acad. Sci. USA 1992, 89, 11612-11616.
105. Ladel, C.H.; Flesch, I.E.; Arnoldi, J.; Kaufmann, S.H. Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection. J. Immunol. 1994, 153, 3116-3122.
106. Gekara, N.O.; Zietara, N.; Geffers, R.; Weiss, S. Listeria monocytogenes induces T cell receptor unresponsiveness through pore-forming toxin listeriolysin O. J. Infect. Dis. 2010, 202, 1698-1707.
107. Carrero, J.A.; Calderon, B.; Unanue, E.R. Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule. J. Immunol. 2004, 172, 4866-4874.