Chapter 24 : spp.: Masters of Inflammation

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This chapter highlights recent progress made toward understanding the molecular basis of -induced enteritis. Information is scarce on the specific course of events following nontyphoidal infection in humans because most infected individuals are rarely hospitalized. As such, observations of nontyphoidal infection have mostly come from patients admitted to the hospital with severe fatal infections. Interactions between bacteria and intestinal tissue were examined in starved, opium-treated guinea pigs several hours after oral challenge with 10 invasive serovar Typhimurium. This study found that closely contacts the epithelial cells lining the intestine, primarily the ileum, and thereafter elicits the local degeneration of filamentous actin in apical microvilli and the underlying terminal web. More recently, studies have turned to the use of cattle to model the pathophysiology of -induced enteritis in humans. Following nitrogen mustard administration, the rabbit ligated ileal loops were then infected with serovar Typhimurium for 72 h. Results from this study revealed that nitrogen mustard treatment markedly inhibited serovar Typhimurium-induced secretion. This inflammatory response greatly contributes to the pathophysiology of the infection, exhibited by typical inflammatory diarrhea. Recent work has begun to disclose the molecular and cellular events involved in this complex phenomenon. In addition to TTSS-1-associated genes, several other genes affecting enteropathogenicity are currently being investigated.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 1

Cl secretory pathways induced by during infection. The intracellular SopB protein affects inositol phosphate (IP) signaling events. One such event is the transient increase in IP4, which antagonizes the closure of chloride channels influencing net electrolyte transport and, hence, fluid secretion. Infection of epithelial cells also results in the production of PGs such as PGE, which can further lead to Cl secretion. Finally, Cl release can be initiated by apically located and activated PMN. These PMN release 5′-AMP, which, through a series of steps, triggers signaling cascades involving cyclic AMP and thus promotes the opening of apical Cl channels.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 2

Model of proposed events affecting -induced PMN transmigration across the intestinal epithelium. spp. evoke a potent inflammatory response in the host, the hallmark of which is the migration of PMN across the intestinal mucosa. This process includes extravasation of circulating PMN from the microvasculature, passage of PMN across the lamina propria, and paracellular movement of PMN across the epithelium. PMN recruitment is coordinated by the release of proinflammatory cytokines, among which are IL-8 and PEEC. interaction with enterocytes delivers Sop proteins into the cell cytoplasm via a TTS-dependent pathway. These Sop proteins play a role in enteropathogenic responses in the intestinal mucosa. Intracellular bacteria reside within membrane-bound vesicles and possibly continue to translocate TTSS-1-secreted effectors. By an unknown mechanism, invasion also causes the transcellular transport of flagellin to the basolateral membrane domain, where it promotes the release of IL-8 by interacting with TLR-5. Concurrently, the TTSS-1 product, SipA, was found to be both necessary and sufficient for induction of PMN transmigration across model intestinal epithelia in a PKC-dependent manner.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 3

Model of serovar Typhimurium-induced signaling in epithelial cells by the -secreted protein SipA. Interaction of the serovar Typhimuriumsecreted effector protein SipA with the apical domain of polarized epithelial cells leads to activation of ARF6 (GTP-ARF6) at the apical membrane, most likely through the mammalian guanine exchange factor (GEF) ARNO. This leads to an increase in PLD activity and local production of PA, which is metabolized to DAG by PA phosphohydrolase (PAP). Generation of DAG recruits PKC to the apical membrane. Activation of PKC at this site (PKC) is necessary for the apical release of the chemokine PEEC and subsequent basolateral-to-apical PMN transmigration.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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1. Ahmer, B. M.,, J. van Reeuwijk,, P. R. Watson,, T. S. Wallis,, and F. Heffron. 1999. Salmonella SirA is a global regulator of genes mediating enteropathogenesis. Mol. Microbiol. 31: 971 982.
2. Altschuler, Y.,, S. Liu,, L. Katz,, K. Tang,, S. Hardy,, F. Brodsky,, G. Apodacca,, and K. Mostov. 1999. ADP-ribosylation factor 6 and endocytosis at the apical surface of Madin-Darby canine kidney cells. J. Cell Biol. 147: 7 12.
3. Amin, B. M.,, G. R. Douce,, M. P. Osborne,, and J. Stephen. 1994. Quantitative studies of invasion of rabbit ileal mucosa by Salmonella typhimurium strain which differ in virulence in model gastroenteritis. Infect. Immun. 62: 569 578.
4. Baggiolini, M.,, B. Dewald,, and A. Walz,. 1992. Interleukin-8 and related cytokines, p. 247 263. In J. I. Gallin,, I. M. Golstein,, and R. Snyderman (ed.), Inflammation: Basic Principles and Clinical Correlates, 2nd ed. Raven Press, New York, N.Y.
5. Bolton, A. J.,, M. P. Osborne,, T. S. Wallis,, and J. Stephen. 1999. Interaction of Salmonella cholersuis, Salmonella dublin, and Salmonella typhimurium with porcine and bovine terminal ileum in vivo. Microbiology 145: 2431 2441.
6. Boyd, J. E. 1985. Pathology of the alimentary tract in Salmonella typhimurium food poisoning. Gut 26: 935 944.
7. Criss, A. K.,, M. Silva,, J. E. Casanova,, and B. A. McCormick. 2001. Regulation of Salmonella-induced neutrophil transmigration by epithelial ADP-ribosylation factor 6. J. Biol. Chem. 276: 48431 48439.
8. Day, D. W.,, B. K. Mandal,, and B. C. Morson. 1978. The rectal biopsy appearances in Salmonella colitis. Histopathology 2: 117 131.
9. Dharmsathaphorn, K.,, and J. L. Madara. 1990. Established intestinal cell lines as model systems for electrolyte transport studies. Methods Enzymol. 192: 354 389.
10. D’Souza-Shorey, C.,, G. Li,, M. I. Colombo,, and P. D. Stahl. 1995. A regulatory role for ARF6 in receptor-mediated endocytosis. Science 267: 1175 1178.
11. Eaves-Pyles, T.,, K. Murthy,, L. Liaudet,, L. Virag,, G. Ross,, F. G. Soriano,, C. Szabo,, and A. L. Salzman. 2001. Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction. J. Immunol. 166: 1248 1260.
12. Eberhart, C. E.,, and R. N. DuBois. 1995. Eicosanoids and the gastrointestinal tract. Gastroenterology 109: 285 301.
13. Eckmann, L.,, H.-C. Jung,, C.-C. Schuerer-Maly,, A. Panja,, E. MorzyckaWroblewska,, and M. F. Kagnoff. 1993. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin-8. Gastroenterology 105: 1689 1697.
14. Eckmann, L.,, M. T. Rudolf,, A. Ptasznik,, C. Schultz,, T. Jiang,, N. Wolfson,, R. Tsein,, J. Fierer,, S. Shears,, M. F. Kagnoff,, and A. E. Traynor-Kaplan. 1997. D-Myo-inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways. Proc. Natl. Acad. Sci. USA 94: 14456 14460.
15. Eckmann, L.,, W. F. Stenson,, T. C. Savidge,, D. C. Lowe,, K. E. Barrett,, J. Fierer,, J. R. Smith,, and M. F. Kagnoff. 1997. Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. J. Clin. Investig. 100: 296 309.
16. Feng, Y.,, S. R. Wente,, and P. W. Majerus. 2001. Overexpression of the inositol phosphate SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export. Proc. Natl. Acad. Sci. USA 98: 875 879.
17. Finlay, B. B.,, S. Ruschkowski,, and S. Dedhar. 1991. Cytoskeletal arrangements accompanying Salmonella entry into epithelial cells. J. Cell Sci. 99: 283 296.
18. Galan, J. E. 1996. Molecular genetic bases of Salmonella entry into host cells. Mol. Microbiol. 20: 263 271.
19. Galyov, E. G.,, M. W. Wood,, R. Rosqvist,, P. B. Mullan,, P. R. Watson,, S. Hedges,, and T. S. Wallis. 1997. A secreted effector protein of Salmonella dublin is translocated into eucaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol. Microbiol. 25: 903 912.
20. Gewirtz, A. T.,, A. M. Siber,, J. L. Madara,, and B. A. McCormick. 1999. Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization. Infect. Immun. 67: 608 617.
21. Gewirtz, A. T.,, A. S. Rao,, P. O. Simon,, 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- кB pathway. J. Clin. Investig. 105: 79 92.
22. Gewirtz, A. T.,, A. T. Navas,, S. Lyons,, P. J. Godowski,, and J. L. Madara. 2001. Bacterial flagella activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167: 1882 1885.
23. Gewirtz, A. T.,, P. O. Simon,, C. K. Schmitt,, L. J. Taylor,, C. H. Hagedorn,, A. D. O’Brien,, A. S. Neish,, and J. L. Madara. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J. Clin. Investig. 107: 99 109.
24. Gianella, R. A.,, S. B. Formal,, G. J. Dammin,, and H. Collins. 1973. Pathogenesis of salmonellosis: studies of fluid secretion, mucosal invasion, and morphologic reaction in the rabbit ileum. J. Clin. Investig. 52: 441 453.
25. Gianella, R. A. 1979. Importance of intestinal inflammatory reaction in Salmonella-mediated intestinal secretion. Infect. Immun. 23: 140 145.
26. Hayashi, F.,, K. D. Smith,, A. Ozinsky,, T. R. Hawn,, E. C. Yi,, D. R. Goodlett,, J. K. Eng,, S. Akira,, D. M. Underhill,, and A. Aderem. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099 1103.
27. Hobbie, S.,, L. M. Chen,, R. J. Davis,, and J. E. Galan. 1997. Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured epithelial cells. J. Immunol. 159: 5550 5559.
28. Hong, K. H.,, and V. L. Miller. 1998. Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE. J. Bacteriol. 180: 1793 1802.
29. Hueck, C. J. 1998. Type III secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62: 379 433.
30. Iyoda, S.,, T. Kamidoi,, K. Hirose,, K. Kutsukake,, and H. Watanabe. 2001. A flagellar gene fliz regulates the expression of invasion genes and virulence phenotype in Salmonella enterica serovar Typhimurium. Microb. Pathog. 30: 81 90.
31. Jones, M. A.,, M. W. Wood,, P. B. Mullan,, P. R. Watson,, T. S. Watson,, and E. E. Galyov. 1998. Secreted effector proteins of Salmonella dublin act in concert to induce enteritis. Infect. Immun. 66: 5799 5804.
32. Jung, H. C.,, L. Eckmann,, S.-K. Yang,, A. Panja,, J. Fierer,, E. Morzycka-Wroblewska,, and M. F. Kagnoff. 1995. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J. Clin. Investig. 95: 55 65.
33. Kumar, N. B.,, T. T. Nostrant,, and H. D. Appelman. 1982. The histopathologic spectrum of acute self-limited colitis (acute infectious type colitis). Am. J. Surg. Pathol. 6: 523 529.
34. Lee, C. A.,, M. Silva,, A. M. Siber,, A. J. Kelly,, E. Galyov,, and B. A. McCormick. 2000. A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration. Proc. Natl. Acad. Sci. USA 97: 12283 12288.
35. Londono, I.,, V. Marshansky,, S. Bourgoin,, P. Vinay,, and M. Bendayan. 1999. Expression and distribution of adenosine diphosphate ribosylation factors in the rat kidney. Kidney Int. 55: 1407 1416.
36. Madara, J. L.,, T. W. Patapoff,, B. Gillece-Castro,, S. P. Colgan,, C. A. Parkos,, C. Delp,, and R. J. Mrsny. 1993. 5′-Adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers. J. Clin. Investig. 91: 2320 2325.
37. Makishima, S.,, K. Komoriya,, S. Yamaguchi,, and S. I. Aizawa. 2001. Length of the flagella hook and the capacity of the type III export apparatus. Science 291: 2411 2413.
38. McCormick, B.,, P. Hofman,, J. Kim,, D. Carnes,, S. Miller,, and J. Madara. 1995. Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils. J. Cell Biol. 131: 1599 1608.
39. McCormick, B.,, S. Miller,, D. Carnes,, and J. Madara. 1995. Transepithelial signaling to neutrophils by Salmonellae: a novel virulence mechanism for gastroenteritis. Infect. Immun. 63: 2302 2309.
40. McCormick, B. A.,, S. P. Colgan,, C. D. Archer,, S. I. Miller,, and J. L. Madara. 1993. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J. Cell Biol. 123: 895 907.
41. McCormick, B. A.,, C. A. Parkos,, S. P. Colgan,, D. K. Carnes,, and J. L. Madara. 1998. Apical secretion of a pathogen-elicited epithelial chemoattractant (PEEC) activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium. J. Immunol. 160: 455 466.
42. McGovern, V. J.,, and L. J. Slavutin. 1979. Pathology of Salmonella colitis. Am. J. Surg. Pathol. 3: 483 490.
43. Norris, A. F.,, M. P. Wilson,, T. S. Wallis,, E. E. Galyov,, and P. W. Majerus. 1998. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc. Natl. Acad. Sci. USA 95: 14057 14059.
44. Rout, W. R.,, S. B. Formal,, G. J. Dammin,, and R. A. Giannella. 1974. Pathophysiology of Salmonella diarrhea in the rhesus monkey: intestinal transport, morphological and bacteriological studies. Gastroenterology 67: 59 70.
45. Sitaraman, S. V.,, D. Merlin,, L. Wang,, M. Wong,, A. T. Gewirtz,, M. Si-Tahar,, and J. L. Madara. 2001. Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6. J. Clin. Investig. 107: 861 869.
46. Smith, W. L.,, and D. L. DeWitt. 1996. Prostaglandin endoperoxidase H synthase-1 and -2. Adv. Immunol. 62: 167 215.
47. Steele-Mortimer, O.,, S. Meresse,, J. P. Gorval,, B. H. Toh,, and B. B. Finlay. 1999. Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interaction with the early endocytic pathway. Cell Microbiol. 1: 33 49.
48. Steiner, T. S.,, J. P. Nataro,, C. E. Poteet-Smith,, J. A. Smith,, and R. L. Guerrant. 2000. Enteroaggregative Escherchia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells. J. Clin. Investig. 105: 1769 1777.
49. Strohmeier, G. R.,, S. M. Reppert,, W. L. Lencer,, and J. L. Madara. 1995. The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. J. Biol. Chem. 270: 2387 2394.
50. Takeuchi, A. 1967. Electron microscope studies of experimental Salmonella infection. Am. J. Pathol. 50: 109 119.
51. Tsolis, R. M.,, G. Adams,, T. A. Ficht,, and A. J. Baumler. 1999. Contribution of Salmonella typhimurium virulence factors to diarrheal disease in calves. Infect. Immun. 67: 4879 4885.
52. Venkateswarlu, K.,, and P. J. Cullen. 2000. Signalling via ADP-ribosylation factor 6 lies downstream of phosphatidylinositide 3-kinase. Biochem. J. 345: 719 724.
53. Wallis, T. S.,, W. G. Starkey,, J. Stephen,, M. P. Osborne,, and D. C. A. Candy. 1986. The nature and role of mucosal damage in relation to Salmonella typhimurium-induced fluid secretion in the rabbit ileum. J. Med. Microbiol. 22: 39 49.
54. Wallis, T. S.,, A. T. M. Vaughan,, G. J. Clarke,, G.-M. Qi,, K. J. Woron,, D. C. A. Candy,, M. P. Osborne,, and J. Stephen. 1990. The role of leucocytes in the induction of fluid secretion by Salmonella typhimurium. J. Med. Microbiol. 31: 27 35.
55. Wallis, T. S.,, S. M. Paulin,, J. S. Plested,, P. R. Watson,, and P. W. Jones. 1995. The Salmonella dublin virulence plasmid mediates systemic but not enteric phases of salmonellosis in cattle. Infect. Immun. 63: 2755 2761.
56. Wallis, T. S.,, and E. E. Galyov. 2000. Molecular basis of Salmonella-induced enteritis. Mol. Microbiol. 36: 997 1005.
57. Watson, P. R.,, S. M. Paulin,, A. P. Bland,, P. W. Jones,, and T. S. Wallis. 1995. Characterization of intestinal invasion by Salmonella typhimurium and Salmonella dublin and effect of a mutation in the invH gene. Infect. Immun. 63: 2743 2754.
58. Watson, P. R.,, E. E. Galyov,, S. M. Paulin,, P. W. Jones,, and T. S. Wallis. 1998. Mutation of invH, but not stn, reduces Salmonella-induced enteritis in cattle. Infect. Immun. 66: 1432 1438.
59. Watson, P. R.,, S. M. Paulin,, A. P. Bland,, P. W. Jones,, and T. S. Wallis. 1999. Differential regulation of enteric and systemic salmonellosis by slyA. Infect. Immun. 67: 4950 4954.
60. Wood, M. W.,, R. Rosqvist,, P. B. Mullan,, M. H. Edwards,, and E. E. Galyov. 1996. SopE, a secreted protein of Salmonella dublin, is translocated into the target eukaryotic cell via a sip-dependent mechanism and promotes bacterial entry. Mol. Microbiol. 22: 327 338.
61. Wood, M. W.,, M. A. Jones,, P. R. Watson,, S. Hedges,, T. S. Wallis,, and E. E. Galyov. 1998. Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol. Microbiol. 29: 883 892.
62. Wood, M. W.,, M. A. Jones,, P. R. Watson,, A. M. Siber,, B. A. McCormick,, S. Hedges,, R. Rosqvist,, T. S. Wallis,, and E. E. Galyov. 2000. The secreted effector protein of Salmonella dublin, SopA, is translocated into eukaryotic cells and influences the induction of enteritis. Cell Microbiol. 2: 293 303.
63. Young, G. M.,, D. H. Schiel,, and V. L. Miller. 1999. A new pathway for the secretion of virulence factors by bacteria: the flagellar export apparatus functions as a protein secretion system. Proc. Natl. Acad. Sci. USA 96: 6456 6461.
64. Zhou, D.,, L. M. Chen,, L. Hernandez,, S. B. Shears,, and J. E. Galan. 2001. A Salmonella inositol polyphosphate acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39: 248 259.

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