Chapter 25 : The Role of Phagocytic Cells during Invasion of the Colonic Mucosa

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In acute shigellosis, bacterial invasion of the colonic mucosa is characterized by the development of an intense inflammatory reaction that is responsible for tissue destruction. This chapter reviews the role of determinants with an emphasis on the role of phagocytic cells during the establishment of infection. There are no animal models that faithfully reproduce the disease, and consequently the sequence of events leading to bacterial invasion of the colonic mucosa and to the mounting of the inflammatory reaction in its natural host is not precisely known. Although the infected tissue is not related to the colonic mucosa, this model has proven very useful to decipher cytokine profiles and immune responses induced during infection and benefits from the availability of mice genetically impaired for specific pathways. In light of the importance in downregulating inflammation, and given the importance of phagocytic cells in the control of inflammation, it is possible that the function of some T3S effectors, in particular, the second-line subset of effectors, target-specific cell types. Paradoxically, extracellular release of ATP was shown to favor invasion and dissemination in neighboring epithelial cells.

Citation: Tran Van Nhieu G, Sansonetti P. 2009. The Role of Phagocytic Cells during Invasion of the Colonic Mucosa, p 405-418. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch25
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Phagocytic cells and invasion of the colonic epithelium. (1) invasion is not efficient at the apical side of enterocytes but may occur occasionally, leading to the release of IL-8, which acts as a chemoattractant for PMNs. These discrete events account for successful invasion or bacterial crossing of the epithelium. (2) invasions preferentially occur at the levels of M cells overlying solitary lymphoid follicles. Bacterial phagocytosis by macrophages results in cell death and the release of IL-1β and IL-18 which, in turn, trigger the recruitment of PMNs at the site of infection. The influx of incoming PMNs destabilizes the epithelium, favoring access to the enterocyte’s basal side, where invasion readily occurs. (3) Destruction of the epithelium following bacterial invasion, replication, and dissemination in enterocytes is determined by the proinflammatory action of PMNs and macrophages. DC, dendritic cell.

Citation: Tran Van Nhieu G, Sansonetti P. 2009. The Role of Phagocytic Cells during Invasion of the Colonic Mucosa, p 405-418. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch25
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The arsenal of T3S effectors. (Inset) T3S effectors can be divided into (1) constitutively expressed early effectors that are injected following cell contact—among these, the IpaB and IpaC proteins insert into host cell membranes to form the “translocon”; (2) effectors that are upregulated after secretion; and (3) late effectors that are only expressed after T3S has been induced. (EARLY) T3S effectors that promote bacterial invasion include IpaC, which induces actin polymerization; IpgB1, which activates the Dock/ELMO pathway; and IpaA, which binds to vinculin and induces actin depolymerization. IpgB2 is a mimic of the GTPase Rho. IpgD hydrolyzes PI(4,5)P2 and activates the PI3-K/Akt pathway. VirA inhibits microtubule polymerization and favors intracellular actin-based motility. IcsB binds to Atg5 and prevents autophagy. The early stages of invasion are associated with proinflammatory signals since intracellular PG stimulates Nod1-dependent activation of NF-κB. invasion also induces Ca signaling and the release of extracellular ATP through hemichannels. (LATE) Late T3S effectors down-regulate inflammatory signals. OspG binds to UbcH5, a E2 ubiquitin-conjugating enzyme, and prevents degradation of I-κB by the proteasome. OspF inhibits the activation of the MAPKs Erk2 and p38. OspF also alters the histone code by inhibiting the phosphorylation of histone H3. IpaH9.8 is an E3 ubiquitin ligase that may target the degradation of a MAPK by the proteasome.

Citation: Tran Van Nhieu G, Sansonetti P. 2009. The Role of Phagocytic Cells during Invasion of the Colonic Mucosa, p 405-418. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch25
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and phagocytes: cell or bacterial killing. internalization by the macrophage leads to cell death. Bacterial-induced apoptosis dependent on caspase 1/IpaB leads to the release of IL-1β and IL-18. The ASC-containing IPAF inflammasome may be involved in this process. Alternatively, macrophages may die of caspase-1-independent necrosis linked to T3S-dependent plasma membrane permeabilization, potentially mediated by the targeting of mitochondria by invasive bacteria. Necrosis was also reported to result from the release of lipid A by intracellular bacteria. Neutrophils (PMNs) kill internalized through the fusion of elastase-containing granules with the phagocytic vacuole. The activation of the NADPH oxidase and the production of reactive oxygen species (ROS) trigger the formation of neutrophil extracellular traps with PMN postmortem bactericidal activity.

Citation: Tran Van Nhieu G, Sansonetti P. 2009. The Role of Phagocytic Cells during Invasion of the Colonic Mucosa, p 405-418. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch25
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1. Alto, N. M.,, F. Shao,, C. S. Lazar,, R. L. Brost,, G. Chua,, S. Mattoo,, S. A. McMahon,, P. Ghosh,, T. R. Hughes,, C. Boone, and, J.-E. Dixon. 2006. Identification of a bacterial type III effector family with G protein mimicry functions. Cell 124:133145.
2. Arbibe, L.,, D. W. Kim,, E. Batsche,, T. Pedron,, B. Mateescu,, C. Muchardt,, C. Parsot, and, P. J. Sansonetti. 2007. An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses. Nat. Immunol. 8:4756.
3. Ashida, H.,, T. Toyotome,, T. Nagai, and, C. Sasakawa. 2007. Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors. Mol. Microbiol. 63:680693.
4. Bahrani, F. K.,, P. J. Sansonetti, and, C. Parsot. 1997. Secretion of Ipa proteins by Shigella flexneri: inducer molecules and kinetics of activation. Infect. Immun. 65:40054010.
5. Blander, J. M.,, and R. Medzhitov. 2006. On regulation of phagosome maturation and antigen presentation. Nat. Immunol. 7:10291035.
6. Blocker, A.,, P. Gounon,, E. Larquet,, K. Niebuhr,, V. Cabiaux,, C. Parsot, and, P. Sansonetti. 1999. The tripartite type III secretion of Shigella flexneri inserts IpaB and IpaC into host membranes. J. Cell Biol. 147:683693.
7. Blocker, A.,, N. Jouihri,, E. Larquet,, P. Gounon,, F. Ebel,, C. Parsot,, P. Sansonetti, and, A. Allaoui. 2001. Structure and composition of the Shigella flexneri “needle complex,” a part of its type III secretion. Mol. Microbiol. 39:652663.
8. Bougnères, L.,, S. E. Girardin,, S. A. Weed,, A. V. Karginov,, J. C. Olivo-Marin,, J. T. Parsons,, P. J. Sansonetti, and, G. Tran Van Nhieu. 2004. Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells. J. Cell Biol. 166:225235.
9. Bourdet-Sicard, R.,, M. Rudiger,, B. M. Jockusch,, P. Gounon,, P. J. Sansonett, G. Tran Van Nhieu. 1999. Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization. EMBO J. 18:58535862.
10. Brinkmann, V.,, U. Reichard,, C. Goosmann,, B. Fauler,, Y. Uhlemann,, D. S. Weiss,, Y. Weinrauch, and, A. Zychlinsky. 2004. Neutrophil extracellular traps kill bacteria. Science 303:15321535.
11. Buchrieser, C.,, P. Glaser,, C. Rusniok,, H. Nedjari,, H. D’Hauteville,, F. Kunst,, P. Sansonetti, and, C. Parsot. 2000. The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri. Mol. Microbiol. 38:760771.
12. Burton, E. A.,, R. Plattner, and, A. M. Pendergast. 2003. Abl tyrosine kinases are required for infection by Shigella flexneri. EMBO J. 22:54715479.
13. Chen, Y.,, M. R. Smith,, K. Thirumalai, and, A. Zychlinsky. 1996. A bacterial invasin induces macrophage apoptosis by binding directly to ICE. EMBO J. 15:38533860.
14. Cornelis, G. R. 2006. The type III secretion injectisome. Nat. Rev. Microbiol. 4:811825.
15. Cossart, P.,, and P. J. Sansonetti. 2004. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304:242248.
16. Dehio, C.,, M. C. Prevost, and, P. J. Sansonetti. 1995. Invasion of epithelial cells by Shigella flexneri induces tyrosine phosphorylation of cortactin by a pp60c-src-mediated signalling pathway. EMBO J. 14:24712482.
17. Demali, K. A.,, A. L. Jue, and, K. Burridge. 2006. IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry. J. Biol. Chem. 281:3953439541.
18. Dorman, C. J.,, and M. E. Porter. 1998. The Shigella virulence gene regulatory cascade: a paradigm of bacterial gene control mechanisms. Mol. Microbiol. 29:677684.
19. Dumenil, G.,, J. C. Olivo,, S. Pellegrini,, M. Fellous,, P. J. Sansonetti, and, G. Tran Van Nhieu. 1998. Interferon alpha inhibits a Src-mediated pathway necessary for Shigella-induced cytoskeletal rearrangements in epithelial cells. J. Cell Biol. 143:10031012.
20. Dumenil, G.,, P. Sansonetti, and, G. Tran Van Nhieu. 2000. Src tyrosine kinase activity down-regulates Rho-dependent responses during Shigella entry into epithelial cells and stress fibre formation. J. Cell Sci. 113(Pt 1):7180.
21. Edgeworth, J. D.,, J. Spencer,, A. Phalipon,, G. E. Griffin, and, P. J. Sansonetti. 2002. Cytotoxicity and interleukin-1beta processing following Shigella flexneri infection of human monocyte-derived dendritic cells. Eur. J. Immunol. 32:14641471.
22. Egile, C.,, I. Rouiller,, X. P. Xu,, N. Volkmann,, R. Li, and, D. Hanein. 2005. Mechanism of filament nucleation and branch stability revealed by the structure of the Arp2/3 complex at actin branch junctions. PLoS Biol. 3:e383.
23. Enninga, J.,, J. Mounier,, P. Sansonetti, and, G. Tran Van Nhieu. 2005. Secretion of type III effectors into host cells in real time. Nat. Methods 2:959965.
24. Fernandez, I. M.,, M. Silva,, R. Schuch,, W. A. Walker,, A. M. Siber,, A. T. Maurelli, and, B. A. McCormick. 2001. Cadaverine prevents the escape of Shigella flexneri from the phagolysosome: a connection between bacterial dissemination and neutrophil transepithelial signaling. J. Infect. Dis. 184:743753.
25. Fernandez-Prada, C. M.,, D. L. Hoover,, B. D. Tall, and, M. M. Venkatesan. 1997. Human monocyte-derived macrophages infected with virulent Shigella flexneri in vitro undergo a rapid cytolytic event similar to oncosis but not apoptosis. Infect. Immun. 65:14861496.
26. Francois, M.,, V. Le Cabec,, M. A. Dupont,, P. J. Sansonetti, and, I. Maridonneau-Parini. 2000. Induction of necrosis in human neutrophils by Shigella flexneri requires type III secretion, IpaB and IpaC invasions, and actin polymerization. Infect. Immun. 68:12891296.
27. Fritz, J. H.,, R. L. Ferrero,, D. J. Philpott, and, S. E. Girardin. 2006. Nod-like proteins in immunity, inflammation and disease. Nat. Immunol. 7:1250127.
28. Galan, J. E.,, and H. Wolf-Watz. 2006. Protein delivery into eukaryotic cells by type III secretion machines. Nature 444:567573.
29. Gewirtz, A. T.,, A. S. Rao,, P. O. Simon, Jr.,, D. Merlin,, D. Carnes,, J. L. Madara, and, A. S. Neish. 2000. Salmonella typhimurium induces epithelial IL-8 expression via Ca(2+)-mediated activation of the NF-kappaB pathway. J. Clin. Invest. 105:7992.
30. Girardin, S. E.,, and D. J. Philpott. 2004. Mini-review: the role of peptidoglycan recognition in innate immunity. Eur. J. Immunol. 34:17771782.
31. Guichon, A.,, D. Hersh,, M. R. Smith, and, A. Zychlinsky. 2001. Structure-function analysis of the Shigella virulence factor IpaB. J. Bacteriol. 183:12691276.
32. Handa, Y.,, M. Suzuki,, K. Ohya,, H. Iwai,, N. Ishijima,, A. J. Koleske,, Y. Fukui, and, C. Sasakawa. 2007. Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery. Nat. Cell Biol. 9:121128.
33. Izard, T.,, G. Tran Van Nhieu, and, P. R. Bois. 2006. Shigella applies molecular mimicry to subvert vinculin and invade host cells. J. Cell Biol. 175:465475.
34. Jin, Q.,, Z. Yuan,, J. Xu,, Y. Wang,, Y. Shen,, W. Lu,, J. Wang,, H. Liu,, J. Yang,, F. Yang,, X. Zhang,, J. Zhang,, G. Yang,, H. Wu,, D. Qu,, J. Dong,, L. Sun,, Y. Xue,, A. Zhao,, Y. Gao,, J. Zhu,, B. Kan,, K. Ding,, S. Chen,, H. Cheng,, Z. Yao,, B. He,, R. Chen,, D. Ma,, B. Qiang,, Y. Wen,, Y. Hou, and, J. Yu. 2002. Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K-12 and O157. Nucleic Acids Res. 30:44324441.
35. Johnson, S.,, P. Roversi,, M. Espina,, A. Olive,, J. E. Deane,, S. Birket,, T. Field,, W. D. Picking,, A. J. Blocker,, E. E. Galyov,, W. L. Picking, and, S. M. Lea. 2007. Self-chaperoning of the type III secretion system needle tip proteins IpaD and BipD. J. Biol. Chem. 282:40354044.
36. Kim, D. W.,, G. Lenzen,, A. L. Page,, P. Legrain,, P. J. Sansonetti, and, C. Parsot. 2005. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc. Natl. Acad. Sci. USA 102:1404614051.
37. Kohler, H.,, S. P. Rodrigues, and, B. A. McCormick. 2002. Shigella flexneri interactions with the basolateral membrane domain of polarized model intestinal epithelium: role of lipopolysaccharide in cell invasion and in activation of the mitogen-activated protein kinase ERK. Infect. Immun. 70:11501158.
38. Koterski, J. F.,, M. Nahvi,, M. M. Venkatesan, and, B. Haimovich. 2005. Virulent Shigella flexneri causes damage to mitochondria and triggers necrosis in infected human monocyte-derived macrophages. Infect. Immun. 73:504513.
39. Kubori, T.,, A. Sukhan,, S. I. Aizawa, and, J. E. Galan. 2000. Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system. Proc. Natl. Acad. Sci. USA 97:1022510230.
40. Kueltzo, L. A.,, J. Osiecki,, J. Barker,, W. L. Picking,, B. Ersoy,, W. D. Picking, and, C. R. Middaugh. 2003. Structure-function analysis of invasion plasmid antigen C (IpaC) from Shigella flexneri. J. Biol. Chem. 278:27922798.
41. Kuwae, A.,, S. Yoshida,, K. Tamano,, H. Mimuro,, T. Suzuki, and, C. Sasakawa. 2001. Shigella invasion of macrophage requires the insertion of IpaC into the host plasma membrane. Functional analysis of IpaC. J. Biol. Chem. 276:3223032239.
42. Lafont, F.,, G. Tran Van Nhieu,, K. Hanada,, P. Sansonetti, and, F. G. van der Goot. 2002. Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. EMBO J. 21:44494457.
43. Le-Barillec, K.,, J. G. Magalhaes,, E. Corcuff,, A. Thuizat,, P. J. Sansonetti,, A. Phalipon, and, J. P. Di Santo. 2005. Roles for T and NK cells in the innate immune response to Shigella flexneri. J. Immunol. 175:17351740.
44. Lecine, P.,, S. Esmiol,, J. Y. Metais,, C. Nicoletti,, C. Nourry,, C. McDonald,, G. Nunez,, J. P. Hugot,, J. P. Borg, and, V. Ollendorff. 2007. The NOD2-RICK complex signals from the plasma membrane. J. Biol. Chem. 282:1519715207.
45. Li, H.,, H. Xu,, Y. Zhou,, J. Zhang,, C. Long,, S. Li,, S. Chen,, J. M. Zhou, and, F. Shao. 2007. The phosphothreonine lyase activity of a bacterial type III effector family. Science 315:10001003.
46. Lucchini, S.,, H. Liu,, Q. Jin,, J. C. Hinton, and, J. Yu. 2005. Transcriptional adaptation of Shigella flexneri during infection of macrophages and epithelial cells: insights into the strategies of a cytosolic bacterial pathogen. Infect. Immun. 73:88102.
47. Mallett, C. P.,, L. VanDeVerg,, H. H. Collins, and, T. L. Hale. 1993. Evaluation of Shigella vaccine safety and efficacy in an intranasally challenged mouse model. Vaccine 11:190196.
48. Mariathasan, S.,, and D. M. Monack. 2007. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat. Rev. Immunol. 7:3140.
49. Maurelli, A. T.,, R. E. Fernandez,, C. A. Bloch,, C. K. Rode, and, A. Fasano. 1998. “Black holes” and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli. Proc. Natl. Acad. Sci. USA 95:39433948.
50. Mavris, M.,, A. L. Page,, R. Tournebize,, B. Demers,, P. Sansonetti, and, C. Parsot. 2002. Regulation of transcription by the activity of the Shigella flexneri type III secretion apparatus. Mol. Microbiol. 43:15431553.
51. Mayer-Scholl, A.,, P. Averhoff, and, A. Zychlinsky. 2004. How do neutrophils and pathogens interact? Curr. Opin. Microbiol. 7:6266.
52. McCormick, B. A. 2003. The use of transepithelial models to examine host-pathogen interactions. Curr. Opin. Microbiol. 6:7781.
53. McCormick, B. A.,, M. I. Fernandez,, A. M. Siber, and, A. T. Maurelli. 1999. Inhibition of Shigella flexneri-induced transepithelial migration of polymorphonuclear leucocytes by cadaverine. Cell Microbiol. 1:143155.
54. Mounier, J.,, V. Laurent,, A. Hall,, P. Fort,, M. F. Carlier,, P. J. Sansonetti, and, C. Egile. 1999. Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility. J. Cell Sci. 112(Pt 13):20692080.
55. Mounier, J.,, T. Vasselon,, R. Hellio,, M. Lesourd, and, P. J. Sansonetti. 1992. Shigella flexneri enters human colonic Caco-2 epithelial cells through the basolateral pole. Infect. Immun. 60:237248.
56. Nie, H.,, F. Yang,, X. Zhang,, J. Yang,, L. Chen,, J. Wang,, Z. Xiong,, J. Peng,, L. Sun,, J. Dong,, Y. Xue,, X. Xu,, S. Chen,, Z. Yao,, Y. Shen, and, Q. Jin. 2006. Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a. BMC Genomics 7:173.
57. Niebuhr, K.,, S. Giuriato,, T. Pedron,, D. J. Philpott,, F. Gaits,, J. Sable,, M. P. Sheetz,, C. Parsot,, P. J. Sansonetti, and, B. Payrastre. 2002. Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S. flexneri effector IpgD reorganizes host cell morphology. EMBO J. 21:50695078.
58. Nonaka, T.,, T. Kuwabara,, H. Mimuro,, A. Kuwae, and, S. Imajoh-Ohmi. 2003. Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages. Microbiology 149:25132527.
59. Ogawa, M.,, T. Yoshimori,, T. Suzuki,, H. Sagara,, N. Mizushima, and, C. Sasakawa. 2005. Escape of intracellular Shigella from autophagy. Science 307:727731.
60. Ohya, K.,, Y. Handa,, M. Ogawa,, M. Suzuki, and, C. Sasakawa. 2005. IpgB1 is a novel Shigella effector protein involved in bacterial invasion of host cells. Its activity to promote membrane ruffling via Rac1 and Cdc42 activation. J. Biol. Chem. 280:2402224034.
61. Parsot, C. 2005. Shigella spp. and enteroinvasive Escherichia coli pathogenicity factors. FEMS Microbiol. Lett. 252:1118.
62. Parsot, C.,, R. Menard,, P. Gounon, and, P. J. Sansonetti. 1995. Enhanced secretion through the Shigella flexneri MxiSpa translocon leads to assembly of extracellular proteins into macromolecular structures. Mol. Microbiol. 16:291300.
63. Patel, J. C.,, and J. E. Galan. 2006. Differential activation and function of Rho GTPases during Salmonella-host cell interactions. J. Cell Biol. 175:453463.
64. Pendaries, C.,, H. Tronchere,, L. Arbibe,, J. Mounier,, O. Gozani,, L. Cantley,, M. J. Fry,, F. Gaits-Iacovoni,, P. J. Sansonetti, and, B. Payrastre. 2006. PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. EMBO J. 25:10241034.
65. Ramarao, N.,, C. Le Clainche,, T. Izard,, R. Bourdet-Sicard,, E. Ageron,, P. J. Sansonetti,, M. F. Carlier, and, G. Tran Van Nhieu. 2007. Capping of actin filaments by vinculin activated by the Shigella IpaA carboxyl-terminal domain. FEBS Lett. 581:853857.
66. Raqib, R.,, P. K. Moly,, P. Sarker,, F. Qadri,, N. H. Alam,, M. Mathan, and, J. Andersson. 2003. Persistence of mucosal mast cells and eosinophils in Shigella-infected children. Infect. Immun. 71:26842692.
67. Raqib, R.,, P. Sarker,, P. Bergman,, G. Ara,, M. Lindh,, D. A. Sack,, K. M. Nasirul Islam,, G. H. Gudmundsson,, J. Andersson, and, B. Agerberth. 2006. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc. Natl. Acad. Sci. USA 103:91789183.
68. Rohde, R.,, A. Breikreutz,, A. Chenal,, P. Sansonetti, and, C. Parsot. 2007. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbes 1:7783.
69. Sani, M.,, A. Botteaux,, C. Parsot,, P. Sansonetti,, E. J. Boekema, and, A. Allaoui. 2007. IpaD is localized at the tip of the Shigella flexneri type III secretion apparatus. Biochim. Biophys. Acta 1770:307311.
70. Sansonetti, P. J.,, T. L. Hale,, G. J. Dammin,, C. Kapfer,, H. H. Collins, Jr., and, S. B. Formal. 1983. Alterations in the pathogenicity of Escherichia coli K-12 after transfer of plasmid and chromosomal genes from Shigella flexneri. Infect. Immun. 39:13921402.
71. Sansonetti, P. J.,, and A. Phalipon. 1999. M cells as ports of entry for enteroinvasive pathogens: mechanisms of interaction, consequences for the disease process. Semin. Immunol. 11:193203.
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-1beta and IL-18 are essential for Shigella flexneri-induced inflammation. Immunity 12:581590.
73. Sansonetti, P. J.,, G. Tran Van Nhieu, and, C. Egile. 1999. Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella flexneri. Clin. Infect. Dis. 28:466475.
74. Schroeder, G. N.,, and H. Hilbi. 2007. Cholesterol is required to trigger caspase-1 activation and macrophage apoptosis after phagosomal escape of Shigella. Cell. Microbiol. 9:265278.
75. Sereny, B.,, C. Tenner, and, P. Racz. 1971. Immunogenicity of living attenuated shigellae. Acta Microbiol. Acad. Sci. Hung. 18:239245.
76. Skoudy, A.,, J. Mounier,, A. Aruffo,, H. Ohayon,, P. Gounon,, P. Sansonetti, and, G. Tran Van Nhieu. 2000. CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells. Cell. Microbiol. 2:1933.
77. Sutterwala, F. S.,, Y. Ogura, and, R. A. Flavell. 2007. The inflammasome in pathogen recognition and inflammation. J. Leukoc. Biol. 82:259264.
78. Suzuki, T.,, K. Nakanishi,, H. Tsutsui,, H. Iwai,, S. Akira,, N. Inohara,, M. Chamaillard,, G. Nunez, and, C. Sasakawa. 2005. A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages. J. Biol. Chem. 280:1404214050.
79. Tehrani, S.,, N. Tomasevic,, S. Weed,, R. Sakowicz, and, J. A. Cooper. 2007. Src phosphorylation of cortactin enhances actin assembly. Proc. Natl. Acad. Sci. USA 104:1193311938.
80. Tran Van Nhieu, G.,, E. Caron,, A. Hall, and, P. J. Sansonetti. 1999. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J. 18:32493262.
81. Tran Van Nhieu, G.,, C. Clair,, R. Bruzzone,, M. Mesnil,, P. Sansonetti, and, L. Combettes. 2003. Connexin-dependent intercellular communication increases invasion and dissemination of Shigella in epithelial cells. Nat. Cell Biol. 5:720726.
82. Tran Van Nhieu, G.,, J. Enninga,, P. Sansonetti, and, G. Grompone. 2005. Tyrosine kinase signaling and type III effectors orchestrating Shigella invasion. Curr. Opin. Microbiol. 8:1620.
83. Uematsu, S.,, and S. Akira. 2006. Innate immunity and toll-like receptor. Nippon Naika Gakkai Zasshi 95:11151121.
84. Ulevitch, R. J.,, J. C. Mathison, and, J. da Silva Correia. 2004. Innate immune responses during infection. Vaccine 22(Suppl 1):S25S30.
85. Veenendaal, A. K.,, J. L. Hodgkinson,, L. Schwarzer,, D. Stabat,, S. F. Zenk, and, A. J. Blocker. 2007. The type III secretion system needle tip complex mediates host cell sensing and translocon insertion. Mol. Microbiol. 63:17191730.
86. Weaver, A. M.,, A. V. Karginov,, A. W. Kinley,, S. A. Weed,, Y. Li,, J. T. Parsons, and, J. A. Cooper. 2001. Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr. Biol. 11:370374.
87. Weaver, A. M.,, M. E. Young,, W. L. Lee, and, J. A. Cooper. 2003. Integration of signals to the Arp2/3 complex. Curr. Opin. Cell Biol. 15:2330.
88. Wei, J.,, M. B. Goldberg,, V. Burland,, M. M. Venkatesan,, W. Deng,, G. Fournier,, G. F. Mayhew,, G. Plunkett, III,, D. J. Rose,, A. Darling,, B. Mau,, N. T. Perna,, S. M. Payne,, L. J. Runyen-Janecky,, S. Zhou,, D. C. Schwartz, and, F. R. Blattner. 2003. Complete genome sequence and comparative genomics of Shigella flexneri serotype 2a strain 2457T. Infect. Immun. 71:27752786.
89. Weinrauch, Y.,, D. Drujan,, S. D. Shapiro,, J. Weiss, and, A. Zychlinsky. 2002. Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:9194.
90. Wenneras, C.,, P. Ave,, M. Huerre,, J. Arondel,, R. J. Ulevitch,, J. C. Mathison, and, P. Sansonetti. 2000. Blockade of CD14 increases Shigella-mediated invasion and tissue destruction. J. Immunol. 164:32143221.
91. Yoshida, S.,, Y. Handa,, T. Suzuki,, M. Ogawa,, M. Suzuki,, A. Tamai,, A. Abe,, E. Katayama, and, C. Sasakawa. 2006. Microtubule-severing activity of Shigella is pivotal for intercellular spreading. Science 314:985989.
92. Yoshida, S.,, E. Katayama,, A. Kuwae,, H. Mimuro,, T. Suzuki, and, C. Sasakawa. 2002. Shigella delivers an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization. EMBO J. 21:29232935.
93. Zasloff, M. 2006. Inducing endogenous antimicrobial peptides to battle infections. Proc. Natl. Acad. Sci. USA 103:89138914.
94. Zhang, Z.,, L. Jin,, G. Champion,, K. B. Seydel, and, S. L. Stanley, Jr. 2001. Shigella infection in a SCID mouse-human intestinal xenograft model: role for neutrophils in containing bacterial dissemination in human intestine. Infect. Immun. 69:32403247.
95. Zychlinsky, A.,, B. Kenny,, R. Menard,, M. C. Prevost,, I. B. Holland, and, P. J. Sansonetti. 1994. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol. Microbiol. 11:619627.
96. Zychlinsky, A.,, K. Thirumalai,, J. Arondel,, J. R. Cantey,, A. O. Aliprantis, and, P. J. Sansonetti. 1996. In vivo apoptosis in Shigella flexneri infections. Infect. Immun. 64:53575365.

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