Chapter 20 : Apoptosis and Enteric Bacterial Infections

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This chapter summarizes the numerous mechanisms that enteropathogenic bacteria use to induce apoptosis in host cells. It focuses on bacterium induced cell death by three enteric pathogens: , , and . Despite the many mechanistic commonalities shared by these enteric bacteria, the outcome of infection differs considerably. The aim of the chapter is to illustrate how each of the three microbes manages to manipulate the relationship between apoptotic events and pathogenesis according to its individual needs. The integrity of the cell membrane is compromised, resulting in leakage of intracellular contents. In contrast, apoptosis is characterized by cell shrinkage, chromatin condensation, and often loss of contact with adjacent cells. Two of the best characterized cell death receptors are the tumor necrosis factor alpha (TNF-α) receptor (TNF-R) and Fas. These two receptors need to be trimerized in order to signal. and enterohemorrhagic (EHEC), which cause severe diarrheal diseases and hemolytic uremic syndrome (HUS), produce A-B type toxins, called Shiga toxin and Shiga-like toxins or verotoxins, respectively. In enteric infections, toxin-mediated apoptosis preferentially targets epithelial cells, while the bacterial effector proteins interfering with the endogenous death machinery of the cell appear to selectively affect macrophages. The first encounter between bacteria and phagocytes occurs subsequent to ’s traversing the colonic barrier through specialized epithelial cells, called M cells. Many pathogens not only use M cells as their port of entry to the intestinal mucosa, but also have designed strategies to evade elimination by professional phagocytes.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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TLR signaling cascades. Upon activation, TLR recruit the adaptor molecule MyD88, which can initiate two independent outcomes: apoptosis and transcriptional activation. Apoptosis is activated by the initial recruitment of the FADD protein, which recruits the regulatory Casp8. Recruitment of FADD also provokes the maturation of Casp1, which in turns cleaves pro-IL-1 to its active form. Alternatively, MyD88 can recruit IRAK, which through TRAF6 activates MKK and IKK. MKK can phosphorylate JNK, which activates the transcription factor AP-1. Alternatively, IKK phosphorylates and targets I-B (inhibitor of B) to the proteasome, allowing NF-B to migrate to the nucleus and initiate transcription.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 2

Transmission electron micrograph of lymphoid follicles infected with . Virulence of the wild-type strain M90T was assessed in the rabbit ligated ileal loop model. At 8 h post-infection, tissue samples were fixed and processed for transmission electron microscopy. Cells with apoptotic morphology were detected and contain intracellular bacteria (arrowhead). Bar, 1 m. (Reprinted from reference .)

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 3

Casp1 activation by results in inflammation and cell death. After internalization by macrophages, escapes from the phagosome into the cytoplasm of the host cell where it secretes the virulence factor IpaB via a type III secretion system. As a consequence of the direct interaction between IpaB and Casp1, this cysteine protease initiates both an apoptotic cascade leading to cell death and processing and release of the proinflammatory cytokines IL-1 and IL-18, resulting in inflammation.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 4

Pathways of -induced cell death in macrophages. (A) SPI1-dependent cell death occurs rapidly after infection with invasive strains and depends on the interaction between Casp1 and the bacterial effector SipB. As for , SipB-mediated activation of Casp1 leads to the processing of proinflammatory cytokines and cell death. (B) An SPI1-independent mechanism of -induced cell death is observed later after infection. The exact sequence of events leading to macrophage killing is still unclear; however, delayed cell death depends on the -regulated pathogenicity island SPI2 and in part on Casp1.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 5

induces cell death by inhibition of survival pathways and by inducing apoptosis. delivers the effector molecule YopJ into the host cell via type III secretion. YopJ blocks activation of the superfamily of MAPK kinases, thus inactivating both MAPK signaling and NF-B activity. Inhibition of these pathways prevents the cell from producing cytokines and antiapoptotic factors. In addition, can activate the cell death machinery. Whether this process directly involves YopJ is unclear.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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1. Adams, J. M.,, and S. Cory. 1998. The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322 1326.
2. Aliprantis, A. O.,, R. B. Yang,, D. S. Weiss,, P. Godowski,, and A. Zychlinsky. 2000. The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J. 19: 3325 3336.
3. Arondel, J.,, M. Singer,, A. Matsukawa,, A. Zychlinsky,, and P. J. Sansonetti. 1999. Increased interleukin-1 (IL-1) and imbalance between IL-1 and IL-1 receptor antagonist during acute inflammation in experimental shigellosis. Infect. Immun. 67: 6056 6066.
4. Ashkenazi, A.,, and V. M. Dixit. 1998. Death receptors: signaling and modulation. Science 281: 1305 1308.
5. Autenrieth, I. B.,, and J. Heesemann. 1992. In vivo neutralization of tumor necrosis factor alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice. Med. Microbiol. Immunol. 181: 333 338.
6. Baichwal, V. R.,, and P. A. Baeuerle. 1997. Activate NF-κB or die? Curr. Biol. 7: 94 96.
7. Bajaj, V.,, R. L. Lucas,, C. Hwang,, and C. A. Lee. 1996. Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol. Microbiol. 22: 703 714.
8. Boland, A.,, and G. R. Cornelis. 1998. Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection. Infect. Immun. 66: 1878 1884.
9. Buchmeier, N.,, A. Blanc-Potard,, S. Ehrt,, D. Piddington,, L. Riley,, and E. A. Groisman. 2000. A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica. Mol. Microbiol. 35: 1375 1382.
10. Chen, L. M.,, K. Kaniga,, and J. E. Galan. 1996. Salmonella spp. are cytotoxic for cultured macrophages. Mol. Microbiol. 21: 1101 1115.
11. Chen, Y.,, M. R. Smith,, K. Thirumalai,, and A. Zychlinsky. 1996. A bacterial invasin induces macrophage apoptosis by directly binding ICE. EMBO J. 15: 3853 3860.
12. Chen, Z.,, J. Hagler,, V. J. Palombella,, F. Melandri,, D. Scherer,, D. Ballard,, and T. Maniatis. 1995. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 9: 1586 1597.
13. Cookson, B. T.,, and M. A. Brennan. 2001. Pro-inflammatory programmed cell death. Trends Microbiol. 9: 113 114.
14. Cornelis, G. R.,, A. Boland,, A. P. Boyd,, C. Geuijen,, M. Iriarte,, C. Neyt,, M. P. Sory,, and I. Stainier. 1998. The virulence plasmid of Yersinia, an antihost genome. Microbiol. Mol. Biol. Rev. 62: 1315 1352.
15. Darwin, K. H.,, and V. L. Miller. 1999. Molecular basis of the interaction of Salmonella with the intestinal mucosa. Clin. Microbiol. Rev. 12: 405 428.
16. Denecker, G.,, W. Declercq,, C. A. Geuijen,, A. Boland,, R. Benabdillah,, M. van Gurp,, M. P. Sory,, P. Vandenabeele,, and G. R. Cornelis. 2001. Yersinia enterocolitica YopPinduced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid. J. Biol. Chem. 276: 19706 19714.
17. Deng, L.,, C. Wang,, E. Spencer,, L. Yang,, A. Braun,, J. You,, C. Slaughter,, C. Pickart,, and Z. J. Chen. 2000. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103: 351 361.
18. Fantuzzi, G.,, and C. A. Dinarello. 1999. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J. Clin. Immunol. 19: 1 11.
19. Fontaine, A.,, J. Arondel,, and P. J. Sansonetti. 1988. Role of Shiga toxin in the pathogenesis of bacillary dysentery, studied by using a Tox-mutant of Shigella dysenteriae 1. Infect. Immun. 56: 3099 3109.
20. Guilloteau, L. A.,, T. S. Wallis,, A. V. Gautier,, S. MacIntyre,, D. J. Platt,, and A. J. Lax. 1996. The Salmonella virulence plasmid enhances Salmonella-induced lysis of macrophages and influences inflammatory responses. Infect. Immun. 64: 3385 3393.
21. Hatada, E. N.,, D. Krappmann,, and C. Scheidereit. 2000. NF-kappaB and the innate immune response. Curr. Opin. Immunol. 12: 52 58.
22. Hensel, M.,, J. E. Shea,, C. Gleeson,, M. D. Jones,, E. Dalton,, and D. W. Holden. 1995. Simultaneous identification of bacterial virulence genes by negative selection. Science 269: 400 403.
23. Hersh, D.,, D. Monack,, M. Smith,, N. Ghori,, S. Falkow,, and A. Zychlinsky. 1999. The Salmonella invasin SipB induces macrophage apoptosis by binding to Caspase-1. Proc. Natl. Acad. Sci. USA 96: 2396 2401.
24. Hilbi, H.,, J. E. Moss,, D. Hersh,, Y. Chen,, J. Arondel,, S. Banerjee,, R. A. Flavell,, J. Yuan,, P. J. Sansonetti,, and A. Zychlinsky. 1998. Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB. J. Biol. Chem. 273: 32895 32900.
25. Hughes, A. K.,, P. K. Stricklett,, D. Schmid,, and D. E. Kohan. 2000. Cytotoxic effect of Shiga toxin-1 on human glomerular epithelial cells. Kidney Int. 57: 2350 2359.
26. Islam, D.,, B. Veress,, P. K. Bardhan,, A. A. Lindberg,, and B. Christensson. 1997. In situ characterization of inflammatory responses in the rectal mucosae of patients with shigellosis. Infect. Immun. 65: 739 749.
27. Jesenberger, V.,, K. J. Procyk,, J. Yuan,, S. Reipert,, and M. Baccarini. 2000. Salmonellainduced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis. J. Exp. Med. 192: 1035 1046.
28. Jones, B. D.,, and S. Falkow. 1996. Salmonellosis: host immune responses and bacterial virulence determinants. Annu. Rev. Immunol. 14: 533 561.
29. Jones, N. L.,, A. Islur,, R. Haq,, M. Mascarenhas,, M. A. Karmali,, M. H. Perdue,, B. W. Zanke,, and P. M. Sherman. 2000. Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G811 G819.
30. Keenan, K.,, D. Dharpnack,, S. Formal,, and A. O’Brien. 1986. Morphologic evaluation of the effects of Shiga toxin and E. coli Shiga-like toxin on the rabbit intestine. Am. J. Pathol. 125: 69 80.
31. Kerr, J.,, A. Wyllie,, and A. Currie. 1972. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br. J. Cancer 26: 239 257.
32. Kraehenbuhl, J.-P.,, and M. R. Neutra. 1992. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol. Rev. 72: 853 879.
33. Lee, A. K.,, C. S. Detweiler,, and S. Falkow. 2000. OmpR regulates the two-component system SsrA-SsrB in Salmonella pathogenicity island 2. J. Bacteriol. 182: 771 781.
34. Levine, M. M.,, H. L. DuPont,, S. B. Formal,, R. B. Hornick,, A. Takeuchi,, E. J. Gangarosa,, M. J. Snyder,, and J. P. Libonati. 1973. Pathogenesis of Shigella dysenteriae 1 (Shiga) dysentery. J. Infect. Dis. 127: 261 270.
35. Li, P.,, H. Allen,, S. Banerjee,, S. Franklin,, L. Herzog,, C. Johnston,, J. McDowell,, M. Paskind,, L. Rodman,, J. Salfeld,, E. Towne,, D. Tracey,, S. Wardwell,, F.-Y. Wei,, W. Wong,, R. Kamen,, and T. Seshadri. 1995. Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock. Cell 80: 401 411.
36. Li, S. J.,, and M. Hochstrasser. 1999. A new protease required for cell-cycle progression in yeast. Nature 398: 246 251.
37. Libby, S. J.,, M. Lesnick,, P. Hasegawa,, E. Weidenhammer,, and D. G. Guiney. 2000. The Salmonella virulence plasmid spv genes are required for cytopathology in human monocytederived macrophages. Cell Microbiol. 2: 49 58.
38. Lindgren, S. W.,, I. Stojiljkovic,, and F. Heffron. 1996. Macrophage killing is an essential virulence mechanism of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 93: 4197 4201.
39. Los, M.,, S. Wesselborg,, and K. Schulze-Osthoff. 1999. The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice. Immunity 10: 629 639.
40. Mangeney, M.,, C. Lingwood,, S. Taga,, B. Caillou,, T. Tursz,, and J. Wiels. 1993. Apoptosis induced in Burkitt’s lymphoma cells via Gb3/CD77, a glycolipid antigen. Cancer Res. 53: 5314 5319.
41. Marcato, P.,, G. Mulvey,, and G. D. Armstrong. 2002. Cloned Shiga toxin 2 B subunit induces apoptosis in Ramos Burkitt’s lymphoma B cells. Infect. Immun. 70: 1279 1286.
42. Medzhitov, R.,, P. Preston-Hurlburt,, and C. A. Janeway, Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394 397.
43. Medzhitov, R.,, P. Preston-Hurlburt,, E. Kopp,, A. Stadlen,, C. Chen,, S. Ghosh,, and C. A. Janeway, Jr. 1998. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 2: 253 258.
44. Meijer, L. K.,, K. Schesser,, H. Wolf-Watz,, P. Sassone-Corsi,, and S. Pettersson. 2000. The bacterial protein YopJ abrogates multiple signal transduction pathways that converge on the transcription factor CREB. Cell Microbiol. 2: 231 238.
45. Mills, S. D.,, A. Boland,, M.-P. Sory,, P. van der Smissen,, C. Kerbourch,, B. B. Finlay,, and G. R. Cornelis. 1997. Yersinia enterocolitica induces apoptosis in macrophages by a process requiring functional type III secretion and translocation mechanisms and involving YopP, presumably acting as an effector protein. Proc. Natl. Acad. Sci. USA 94: 12638 12643.
46. Monack, D. M.,, C. S. Detweiler,, and S. Falkow. 2001. Salmonella pathogenicity island 2-dependent macrophage death is mediated in part by the host cysteine protease caspase-1. Cell Microbiol. 3: 825 837.
47. Monack, D. M.,, D. Hersh,, N. Ghori,, D. Bouley,, A. Zychlinsky,, and S. Falkow. 2000. Salmonella exploits caspase-1 to colonize Peyer’s patches in a murine typhoid model. J. Exp. Med. 17: 249 258.
48. Monack, D. M.,, J. Mecsas,, D. Bouley,, and S. Falkow. 1998. Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice. J. Exp. Med. 188: 2127 2137.
49. Monack, D. M.,, J. Mecsas,, N. Ghori,, and S. Falkow. 1997. Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc. Natl. Acad. Sci. USA 94: 10385 10390.
50. Monack, D. M.,, B. Raupach,, A. E. Hromockyj,, and S. Falkow. 1996. Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proc. Natl. Acad. Sci. USA 93: 9833 9838.
51. Muller, S.,, M. Berger,, F. Lehembre,, J. S. Seeler,, Y. Haupt,, and A. Dejean. 2000. c-Jun and p53 activity is modulated by SUMO-1 modification. J. Biol. Chem. 275: 13321 13329.
52. Nakajima, R.,, and R. R. Brubaker. 1993. Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect. Immun. 61: 23 31.
53. Neighbors, M.,, X. Xu,, F. J. Barrat,, S. R. Ruuls,, T. Churakova,, R. Debets,, J. F. Bazan,, R. A. Kastelein,, J. S. Abrams,, and A. O’Garra. 2001. A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on interferon gamma production. J. Exp. Med. 194: 343 354.
54. Ninomiya-Tsuji, J.,, K. Kishimoto,, A. Hiyama,, J. Inoue,, Z. Cao,, and K. Matsumoto. 1999. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398: 252 256.
55. Orth, K. 2002. Function of the Yersinia effector YopJ. Curr. Opin. Microbiol. 5: 38 43.
56. Orth, K.,, L. E. Palmer,, Z. Q. Bao,, S. Stewart,, A. E. Rudolph,, J. B. Bliska,, and J. E. Dixon. 1999. Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science 285: 1920 1923.
57. Orth, K.,, Z. Xu,, M. B. Mudgett,, Z. Q. Bao,, L. E. Palmer,, J. B. Bliska,, W. F. Mangel,, B. Staskawicz,, and J. E. Dixon. 2000. Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science 290: 1594 1597.
58. Palmer, L. E.,, S. Hobbie,, J. E. Galan,, and J. B. Bliska. 1998. YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-α production and downregulation of the MAP kinases p38 and JNK. Mol. Microbiol. 27: 953 965.
59. Paton, J. C.,, and A. W. Paton. 1998. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 11: 450 479.
60. Perdomo, O. J.,, J. M. Cavaillon,, M. Huerre,, H. Ohayon,, P. Gounon,, and P. J. Sansonetti. 1994. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J. Exp. Med. 180: 1307 1319.
61. Phalipon, A.,, M. Kaufmann,, P. Michetti,, J. M. Cavaillon,, M. Huerre,, P. Sansonetti,, and J. P. Kraehenbuhl. 1995. Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis. J. Exp. Med. 182: 769 778.
62. Pickart, C. M. 2000. Ubiquitin in chains. Trends Biochem. Sci. 25: 544 548.
63. Richter-Dahlfors, A.,, A. M. J. Buchan,, and B. B. Finlay. 1997. Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo. J. Exp. Med. 186: 569 580.
64. Ruckdeschel, K.,, S. Harb,, A. Roggenkamp,, M. Hornef,, R. Zumbihl,, S. Kohler,, J. Heesemann,, and B. Rouot. 1998. Yersinia enterocolitica impairs activation of transcription factor NF-κB: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor alpha production. J. Exp. Med. 187: 1069 1079.
65. Ruckdeschel, K.,, J. Machold,, A. Roggenkamp,, S. Schubert,, J. Pierre,, R. Zumbihl,, J. P. Liautard,, J. Heesemann,, and B. Rouot. 1997. Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production. J. Biol. Chem. 272: 15920 15927.
66. Ruckdeschel, K.,, O. Mannel,, K. Richter,, C. A. Jacobi,, K. Trulzsch,, B. Rouot,, and J. Heesemann. 2001. Yersinia outer protein P of Yersinia enterocolitica simultaneously blocks the nuclear factor-kappa B pathway and exploits lipopolysaccharide signaling to trigger apoptosis in macrophages. J. Immunol. 166: 1823 1831.
67. Ruckdeschel, K.,, A. Roggenkamp,, V. Lafont,, P. Mangeat,, J. Heesemann,, and B. Rouot. 1997. Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infect. Immun. 65: 4813 4821.
68. Sandvig, K. 2001. Shiga toxins. Toxicon 39: 1629 1635.
69. Sandvig, K.,, and B. van Deurs. 1992. Toxin induced cell lysis: protection by 3-methyladenine and cycloheximide. Exp. Cell Res. 200: 253 262.
70. Sansonetti, P. J.,, J. Arondel,, J. M. Cavaillon,, and M. Huerre. 1995. Role of interleukin-1 in the pathogenesis of experimental shigellosis. J. Clin. Invest. 96: 884 892.
71. Sansonetti, P. J.,, D. J. Kopecko,, and S. B. Formal. 1982. Involvement of a plasmid in the invasive ability of Shigella flexneri. Infect. Immun. 35: 852 860.
72. Sansonetti, P. J.,, A. Phalipon,, J. Arondel,, K. Thirumalai,, S. Banerjee,, S. Akira,, K. Takeda,, and A. Zychlinsky. 2000. Caspase-1 activation of IL-1b and IL-18 are essential for Shigella flexneri induced inflammation. Immunity 12: 581 590.
73. Savill, J.,, and V. Fadok. 2000. Corpse clearance defines the meaning of cell death. Nature 407: 784 788.
74. Schesser, K.,, A. K. Spiik,, J. M. Dukuzumuremyi,, M. F. Neurath,, S. Pettersson,, and H. Wolf-Watz. 1998. The yopJ locus is required for Yersinia-mediated inhibition of NF-κB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol. Microbiol. 28: 1067 1079.
75. Suzuki, A.,, H. Doi,, F. Matsuzawa,, S. Aikawa,, K. Takiguchi,, H. Kawano,, M. Hayashida,, and S. Ohno. 2000. Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible association between bcl-2 and tissue failure by E. coli O157:H7. Genes Dev. 14: 1734 1740.
76. Swain, S. L. 2001. Interleukin 18: tipping the balance towards a T helper cell 1 response. J. Exp. Med. 194: F11 F14.
77. Thirumalai, K.,, K. Kim,, and A. Zychlinsky. 1997. IpaB, a Shigella flexneri invasin, colocalizes with Interleukin-1β converting enzyme (ICE) in the cytoplasm of macrophages. Infect. Immun. 65: 787 793.
78. Thornberry, N. A. 1996. The caspase family of cysteine proteases. Br. Med. Bull. 53: 478 490.
79. Thornberry, N. A.,, H. G. Bull,, J. R. Calaycay,, K. T. Chapman,, A. D. Howard ,, M. J. Kostura,, D. K. Miller,, S. M. Molineaux,, J. R. Weidner,, J. Aunins,, K. O. Elliston,, J. M. Ayala,, F. J. Casano,, J. Chin,, J.-F. Ding,, L. A. Egger,, E. P. Gaffney,, G. Limjuco,, O. C. Palyha,, S. M. Raju,, A. M. Rolando,, J. P. Salley,, T. T. Yamin,, T. D. Lee,, J. E. Shively,, M. MacCross,, R. A. Mumford,, J. A. Schmidt,, and M. J. Tocci. 1992. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 356: 768 774.
80. van der Velden, A. W.,, S. W. Lindgren,, M. J. Worley,, and F. Heffron. 2000. Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype Typhimurium. Infect. Immun. 68: 5702 5709.
81. Wang, C.,, L. Deng,, M. Hong,, G. R. Akkaraju,, J. Inoue,, and Z. J. Chen. 2001. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412: 346 351.
82. Wassef, J. S.,, D. F. Keren,, and J. L. Mailloux. 1989. Role of M cells in initial antigen uptake and in ulcer formation in rabbit intestinal loop model of shigellosis. Infect. Immun. 57: 858 863.
83. Way, S. S.,, A. C. Borczuk,, R. Dominitz,, and M. B. Goldberg. 1998. An essential role for gamma interferon in innate resistance to Shigella flexneri infection. Infect. Immun. 66: 1342 1348.
84. Yamasaki, C.,, Y. Natori,, X. T. Zeng,, M. Ohmura,, S. Yamasaki,, Y. Takeda,, and Y. Natori. 1999. Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1 (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase activity. FEBS Lett. 442: 231 234.
85. Yin, L.,, L. Wu,, H. Wesche,, C. D. Arthur,, J. M. White,, D. V. Goeddel,, and R. D. Schreiber. 2001. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291: 2162 2165.
86. Zychlinsky, A.,, C. Fitting,, J. M. Cavaillon,, and P. J. Sansonetti. 1994. Interleukin-1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J. Clin. Invest. 94: 1328 1332.
87. Zychlinsky, A.,, B. Kenny,, R. Me′nard,, M. C. Pre′vost,, I. B. Holland,, and P. J. Sansonetti. 1994. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol. Microbiol. 11: 619 627.
88. Zychlinsky, A.,, M. C. Pre′vost,, and P. J. Sansonetti. 1992. Shigella flexneri induces apoptosis in infected macrophages. Nature 358: 167 168.
89. Zychlinsky, A.,, and P. J. Sansonetti. 1997. Apoptosis as a proinflammatory event or, what we can learn from bacterial induced cell death. Trends Microbiol. 5: 201 204.
90. Zychlinsky, A.,, K. Thirumalai,, J. Arondel,, J. R. Cantey,, A. Aliprantis,, and P. J. Sansonetti. 1996. In vivo apoptosis in Shigella flexneri infections. Infect. Immun. 64: 5357 5365.

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