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

Key Concept Ranking

Bacterial Proteins
Tumor Necrosis Factor alpha
Type III Secretion System
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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 281:13221326.
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. 19:33253336.
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. 67:60566066.
4. Ashkenazi, A.,, and V. M. Dixit. 1998. Death receptors: signaling and modulation. Science 281:13051308.
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. 181:333338.
6. Baichwal, V. R.,, and P. A. Baeuerle. 1997. Activate NF-κB or die? Curr. Biol. 7:9496.
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. 22:703714.
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. 66:18781884.
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. 35:13751382.
10. Chen, L. M.,, K. Kaniga,, and J. E. Galan. 1996. Salmonella spp. are cytotoxic for cultured macrophages. Mol. Microbiol. 21:11011115.
11. Chen, Y.,, M. R. Smith,, K. Thirumalai,, and A. Zychlinsky. 1996. A bacterial invasin induces macrophage apoptosis by directly binding ICE. EMBO J. 15:38533860.
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. 9:15861597.
13. Cookson, B. T.,, and M. A. Brennan. 2001. Pro-inflammatory programmed cell death. Trends Microbiol. 9:113114.
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. 62:13151352.
15. Darwin, K. H.,, and V. L. Miller. 1999. Molecular basis of the interaction of Salmonella with the intestinal mucosa. Clin. Microbiol. Rev. 12:405428.
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. 276:1970619714.
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 103:351361.
18. Fantuzzi, G.,, and C. A. Dinarello. 1999. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J. Clin. Immunol. 19:111.
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. 56:30993109.
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. 64:33853393.
21. Hatada, E. N.,, D. Krappmann,, and C. Scheidereit. 2000. NF-kappaB and the innate immune response. Curr. Opin. Immunol. 12:5258.
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 269:400403.
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 96:23962401.
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: 3289532900.
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. 57:23502359.
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. 65:739749.
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. 192:10351046.
28. Jones, B. D.,, and S. Falkow. 1996. Salmonellosis: host immune responses and bacterial virulence determinants. Annu. Rev. Immunol. 14:533561.
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:G811G819.
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. 125:6980.
31. Kerr, J.,, A. Wyllie,, and A. Currie. 1972. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br. J. Cancer 26:239257.
32. Kraehenbuhl, J.-P.,, and M. R. Neutra. 1992. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol. Rev. 72:853879.
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. 182:771781.
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. 127:261270.
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 80:401411.
36. Li, S. J.,, and M. Hochstrasser. 1999. A new protease required for cell-cycle progression in yeast. Nature 398:246251.
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. 2:4958.
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 93:41974201.
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 10:629639.
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. 53:53145319.
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. 70:12791286.
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 388:394397.
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 2:253258.
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. 2:231238.
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 94:1263812643.
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. 3:825837.
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. 17:249258.
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. 188:21272137.
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 94:1038510390.
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 93:98339838.
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. 275:1332113329.
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. 61:2331.
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. 194:343354.
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 398:252256.
55. Orth, K. 2002. Function of the Yersinia effector YopJ. Curr. Opin. Microbiol. 5:3843.
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 285:19201923.
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 290:15941597.
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. 27:953965.
59. Paton, J. C.,, and A. W. Paton. 1998. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 11: 450479.
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. 180:13071319.
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. 182:769778.
62. Pickart, C. M. 2000. Ubiquitin in chains. Trends Biochem. Sci. 25:544548.
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. 186:569580.
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. 187:10691079.
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. 272:1592015927.
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. 166:18231831.
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. 65:48134821.
68. Sandvig, K. 2001. Shiga toxins. Toxicon 39: 16291635.
69. Sandvig, K.,, and B. van Deurs. 1992. Toxin induced cell lysis: protection by 3-methyladenine and cycloheximide. Exp. Cell Res. 200:253262.
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. 96:884892.
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. 35:852860.
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 12:581590.
73. Savill, J.,, and V. Fadok. 2000. Corpse clearance defines the meaning of cell death. Nature 407:784788.
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. 28:10671079.
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. 14:17341740.
76. Swain, S. L. 2001. Interleukin 18: tipping the balance towards a T helper cell 1 response. J. Exp. Med. 194:F11F14.
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. 65:787793.
78. Thornberry, N. A. 1996. The caspase family of cysteine proteases. Br. Med. Bull. 53:478490.
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 356:768774.
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. 68:57025709.
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 412:346351.
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. 57:858863.
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. 66:13421348.
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. 442:231234.
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 291:21622165.
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: 13281332.
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. 11:619627.
88. Zychlinsky, A.,, M. C. Pre′vost,, and P. J. Sansonetti. 1992. Shigella flexneri induces apoptosis in infected macrophages. Nature 358:167168.
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. 5:201204.
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. 64:53575365.

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