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The Inflammatory Response during Enterohemorrhagic Infection

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  • Authors: Jaclyn S. Pearson1, Elizabeth L. Hartland2
  • Editors: Vanessa Sperandio4, Carolyn J. Hovde5
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    Affiliations: 1: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia; 2: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia; 3: Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia; 4: University of Texas Southwestern Medical Center, Dallas, TX; 5: University of Idaho, Moscow, ID
  • Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.EHEC-0012-2013
  • Received 28 June 2013 Accepted 26 July 2013 Published 15 August 2014
  • Elizabeth L. Hartland, hartland@unimelb.edu.au
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  • Abstract:

    The inflammatory response is an integral part of host defense against enterohemorrhagic (EHEC) infection and also contributes to disease pathology. In this article we explore the factors leading to inflammation during EHEC infection and the mechanisms EHEC and other attaching and effacing (A/E) pathogens have evolved to suppress inflammatory signaling. EHEC stimulates an inflammatory response in the intestine through host recognition of bacterial components such as flagellin and lipopolysaccharide. In addition, the activity of Shiga toxin and some type III secretion system effectors leads to increased tissue inflammation. Various infection models of EHEC and other A/E pathogens have revealed many of the immune factors that mediate this response. In particular, the outcome of infection is greatly influenced by the ability of an infected epithelial cell to mount an effective host inflammatory response. The inflammatory response of infected enterocytes is counterbalanced by the activity of type III secretion system effectors such as NleE and NleC that modify and inhibit components of the signaling pathways that lead to proinflammatory cytokine production. Overall, A/E pathogens have taught us that innate mucosal immune responses in the gastrointestinal tract during infection with A/E pathogens are highly complex and ultimate clearance of the pathogen depends on multiple factors, including inflammatory mediators, bacterial burden, and the function and integrity of resident intestinal epithelial cells.

  • Citation: Pearson J, Hartland E. 2014. The Inflammatory Response during Enterohemorrhagic Infection. Microbiol Spectrum 2(4):EHEC-0012-2013. doi:10.1128/microbiolspec.EHEC-0012-2013.

Key Concept Ranking

Type III Secretion System
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References

1. Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124:783–801. [PubMed][CrossRef]
2. O'Neill LA, Golenbock D, Bowie AG. 2013. The history of Toll-like receptors—redefining innate immunity. Nat Rev Immunol 13:453–460. [PubMed][CrossRef]
3. Latz E, Xiao TS, Stutz A. 2013. Activation and regulation of the inflammasomes. Nat Rev Immunol 13:397–411. [PubMed][CrossRef]
4. Robins-Browne RM, Hartland EL. 2002. Escherichia coli as a cause of diarrhea. J Gastroenterol Hepatol 17:467–475. [PubMed][CrossRef]
5. Kagnoff MF, Eckmann L. 1997. Epithelial cells as sensors for microbial infection. J Clin Invest 100:6–10. [PubMed][CrossRef]
6. Badea L, Beatson SA, Kaparakis M, Ferrero RL, Hartland EL. 2009. Secretion of flagellin by the LEE- encoded type III secretion system of enteropathogenic Escherichia coli. BMC Microbiol 9:30. [PubMed][CrossRef]
7. Miyamoto Y, Iimura M, Kaper JB, Torres AG, Kagnoff MF. 2006. Role of Shiga toxin versus H7 flagellin in enterohaemorrhagic Escherichia coli signalling of human colon epithelium in vivo. Cell Microbiol 8:869–879. [PubMed][CrossRef]
8. Schuller S, Lucas M, Kaper JB, Giron JA, Phillips AD. 2009. The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infection. Cell Microbiol 11:521–530. [PubMed][CrossRef]
9. Moon HW, Whipp SC, Argenzio RA, Levine MM, Giannella RA. 1983. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines. Infect Immun 41:1340–1351. [PubMed]
10. Tzipori S, Gibson R, Montanaro J. 1989. Nature and distribution of mucosal lesions associated with enteropathogenic and enterohemorrhagic Escherichia coli in piglets and the role of plasmid-mediated factors. Infect Immun 57:1142–1150. [PubMed]
11. Tzipori S, Robins-Browne RM,. Gonis G, Hayes J, Withers M, McCartney E. 1985. Enteropathogenic Escherichia coli enteritis: evaluation of the gnotobiotic piglet as a model of human infection. Gut 26:570–578. [PubMed][CrossRef]
12. Lebeis SL, Bommarius B, Parkos CA,. Sherman MA, Kalman D. 2007. TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium. J Immunol 179:566–577. [PubMed][CrossRef]
13. Slutsker L, Ries A, Greene KD, Wells JG, Hutwagner L, Griffin PM. 1997. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med 126:505–513. [PubMed][CrossRef]
14. Elliott E, Li Z, Bell C, Stiel D, Buret AG, Wallace J, Brzuszczak I, O'loughlin EV. 1994. Modulation of host response to Escherichia coli O157:H7 infection by anti-CD18 antibody in rabbits. Gastroenterology 106:1554–1561. [PubMed]
15. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. 2012. Neutrophil function: from mechanisms to disease. Ann Rev Immunol 30:459–489. [PubMed][CrossRef]
16. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–1535. [PubMed][CrossRef]
17. Phillipson M, Kubes P. 2011. The neutrophil in vascular inflammation. Nat Med 17:1381–1390. [PubMed][CrossRef]
18. Sadik CD, Kim ND, Luster AD. 2011. Neutrophils cascading their way to inflammation. Trends Immunol 32:452–460. [PubMed][CrossRef]
19. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. 2007. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689. [PubMed][CrossRef]
20. Dahan S, Busuttil V, Imbert V, Peyron J-F, Rampal P, Czerucka D. 2002. Enterohemorrhagic Escherichia coli infection induces interleukin-8 production via activation of mitogen-activated protein kinases and the transcription factors NF-κB and AP-1 in T84 cells. Infect Immun 70:2304–2310. [PubMed][CrossRef]
21. Savkovic S, Koutsouris A, Hecht G. 1997. Activation of NF-kappaB in intestinal epithelial cells by enteropathogenic Escherichia coli. Am J Physiol 273:1160–1167. [PubMed]
22. Jung HC, Eckmann L, Yang SK, Panja A, Fierer J, Morzycka-Wroblewska E, Kagnoff MF. 1995. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 95:55–65. [PubMed][CrossRef]
23. McCormick BA, Colgan SP, Delp-Archer C, Miller SI, Madara JL. 1993. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol 123:895–907. [PubMed][CrossRef]
24. Philpott DJ, Yamaoka S, Israel A, Sansonetti PJ. 2000. Invasive Shigella flexneri activates NF-κB through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells. J Immunol 165:903–914. [PubMed][CrossRef]
25. Mukaida N, Mahe Y, Matsushima K. 1990. Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. J Biol Chem 265:21128–21133. [PubMed]
26. Li,Q, Verma IM. 2002. NF-κB regulation in the immune system. Nat Rev Immunol 2:725–734. [PubMed][CrossRef]
27. Ghosh S, May MJ, Kopp EB. 1998. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260. [PubMed][CrossRef]
28. Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. 1995. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev 9:2723–2735. [PubMed][CrossRef]
29. May MJ, Ghosh S. 1998. Signal transduction through NF-κB. Immunol Today 19:80–88. [PubMed][CrossRef]
30. Schulze-Luehrmann J, Ghosh S. 2006. Antigen-receptor signaling to nuclear factor κB. Immunity 25:701–715. [PubMed][CrossRef]
31. Perkins N. 2007. Integrating cell-signaling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol 8:49–62. [PubMed][CrossRef]
32. Mukaida N, Okamoto S, Ishikawa Y, Matsushima K. 1994. Molecular mechanism of interleukin-8 gene expression. J Leuk Biol 56:554–558. [PubMed]
33. Czerucka D, Dahan S, Mograbi B, Rossi B, Rampal P. 2001. Implication of mitogen-activated protein kinases in T84 cell responses to enteropathogenic Esherichia coli infection. Infect Immun 69:1298–1305. [PubMed][CrossRef]
34. de Grado M, Rosenberger CM, Gauthier A, Vallance BA, Finlay BB. 2001. Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells. Infect Immun 69:6217–6224. [PubMed][CrossRef]
35. Davis RJ. 1993. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268:14553–14556. [PubMed]
36. Davis RJ. 2000. Signal transduction by the JNK group of MAP kinases. Cell 103:239–252. [PubMed][CrossRef]
37. Johnson GL, Lapadat R. 2002. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912. [PubMed][CrossRef]
38. Thorpe CM, Hurley BP, Lincicome LL, Jacewicz MS, Keusch GT, Acheson DWK. 1999. Shiga toxins stimulate secretion of interleukin-8 from intestinal epithelial cells. Infect Immun 67:5985–5993. [PubMed]
39. Thorpe CM, Smith WE, Hurley BP, Acheson DWK. 2001. Shiga toxins induce, superinduce, and stabilize a variety of C-X-C chemokine mRNAs in intestinal epithelial cells, resulting in increased chemokine expression. Infect Immun 69:6140–6147. [PubMed][CrossRef]
40. Yamasaki C, Natori Y, Zeng XT, Ohmura M, Yamasaki S, Takeda Y. 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. [PubMed][CrossRef]
41. Berin MC, Darfeuille-Michaud A, Egan LJ, Miyamoto Y, Kagnoff MF. 2002. Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-κB and MAP kinase pathways and the upregulated expression of interleukin 8. Cell Microbiol 4:635–648. [PubMed][CrossRef]
42. Zhou X, Girón JA, Torres AG, Crawford JA, Negrete E, Vogel SN, Kaper JB. 2003. Flagellin of enteropathogenic Escherichia coli stimulates interleukin-8 production in T84 cells. Infect Immun 71:2120–2129. [PubMed][CrossRef]
43. Elliott E, Li Z, Bell C, Stiel D, Buret A, Wallace J, Brzuszczak I, O'Loughlin E. 1994. Modulation of host response to Escherichia coli O157:H7 infection by anti-CD18 antibody in rabbits. Gastroenterology 106:1554–1561. [PubMed]
44. Li Z, Bell C, Buret AG, Robins-Browne RM, Stiel D, O'Loughlin EV. 1993. The effect of enterohemorrhagic Escherichia coli O157:H7 on intestinal structure and solute transport in rabbits. Gastroenterology 104:467–474. [PubMed]
45. Gewirtz AT, Navas TA, Lyons S, Godowski PJ,. Madara JL. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167:1882–1885. [PubMed][CrossRef]
46. McNamara BP, Koutsouris A, O'Connell CB, Nougayrede JP, Donnenberg MS, Hecht G. 2001. Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function. J Clin Invest 107:621–629. [PubMed][CrossRef]
47. Muza-Moons MM, Koutsouris A, Hecht G. 2003. Disruption of cell polarity by enteropathogenic Escherichia coli enables basolateral membrane proteins to migrate apically and to potentiate physiological consequences. Infect Immun 71:7069–7078. [PubMed][CrossRef]
48. Kinnebrew MA, Buffie CG, Diehl GE, Zenewicz LA, Leiner I, Hohl TM, Flavell RA, Littman DR, Pamer EG. 2012. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36:276–287. [PubMed][CrossRef]
49. Phillips A, Frankel G. 2000. Intimin-mediated tissue specificity in enteropathogenic Escherichia coli interaction with human intestinal organ cultures. J Infect Dis 181:1496–1500. [PubMed][CrossRef]
50. Cashman SB, Morgan JG. 2009. Transcriptional analysis of Toll-like receptors expression in M cells. Mol Immunol 47:365–372. [PubMed][CrossRef]
51. Hurley BP, Thorpe CM, Acheson DWK. 2001. Neutrophil translocation across intestinal epithelial cells is enhanced by neutrophil transmigration. Infect Immun 69:6148–6155. [PubMed][CrossRef]
52. Te Loo DM, Hinsbergh VW, Heuvell LP, Monnens LA. 2001. Detection of verotoxin bound to circulationg polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol 12:800–806. [PubMed]
53. Stearns-Kurosawa DJ, Oh S-Y, Cherla RP, Lee M-S, Tesh VL, Papin J, Henderson J, Kurosawa S. 2013. Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli Shiga toxins in non-human primate models of hemolytic uremic syndrome. Am J Pathol 182:1227–1238. [PubMed][CrossRef]
54. Ledesma MA, Ochoa SA, Cruz A, Rocha-Ramirez LM, Mas-Oliva J, Eslava CA, Giron JA, Xicohtencatl-Cortes J. 2010. The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells. PLoS One 5:e12127. [PubMed][CrossRef]
55. Luperchio SA, Schauer DB. 2001. Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic hyperplasia. Microb Infect 3:333–340. [PubMed][CrossRef]
56. Ma C, Wickham ME, Guttman JA, Deng W, Walker J, Madsen KL. 2006. Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map). Cell Microbiol 8:1669–1686. [PubMed][CrossRef]
57. Maaser C, Housley MP, Iimura M, Smith JR, Vallance BA, Finlay BB, Schreiber JR, Varki NM, Kagnoff MF, Eckmann L. 2004. Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies. Infect Immun 72:3315–3324. [PubMed][CrossRef]
58. Simmons CP, Clare S, Ghaem-Maghami M, Uren TK, Rankin J, Huett A, Goldin R, Lewis DJ, MacDonald TT, Strugnell RA, Frankel G, Dougan G. 2003. Central role for B lymphocytes and CD4+ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun 71:5077–5086. [PubMed][CrossRef]
59. Wang Y, Xiang GS, Kourouma F, Umar S. 2006. Citrobacter rodentium-induced NF-κB activation in hyperproliferating colonic epithelia: role of p65 (Ser536) phosphorylation. Br J Pharmacol 148:814–824. [PubMed][CrossRef]
60. Khan MA, Bouzari S, Ma C, Rosenberger CM, Bergstrom KSB, Gibson DL, Steiner TS, Vallance BA. 2008. Flagellin-dependent and -independent inflammatory responses. Infect Immun 76:1410–1422. [PubMed][CrossRef]
61. Wei OL, Hillard A, Kalman D, Sherman MA. 2005. Mast cells limit systemic bacterial dissemenation but not colitis in response to Citrobacter rodentium. Infect Immun 73:1978–1985. [PubMed][CrossRef]
62. Higgins LM, Frankel G, Douce GDougan G, MacDonald TT. 1999. Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease. Infect Immun 67:3031–3039. [PubMed]
63. Geddes K, Rubino SJ, Magalhaes JG, Streutker C, Le Bourhis L, Cho JH, Robertson SJ, Kim CJ, Kaul R, Philpott DJ, Girardin SE. 2011. Identification of an innate T helper type 17 response to intestinal bacterial pathogens. Nat Med 17:837–844. [PubMed][CrossRef]
64. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14:282–289. [PubMed][CrossRef]
65. Gibson DL, Ma A, Rosenberger CM, Bergstrom KSB, Valdez Y, Huang JT, Khan MA, Vallance BA. 2008. Toll-like receptor 2 plays a critical role in maintaining mucosal integrity during Citrobacter rodentium-induced colitis. Cell Microbiol 10:388–403. [PubMed]
66. Eckmann L. 2006. Animal models of inflammatory bowel disease: lessons from enteric infections. Ann New York Acad Sci 1072:28–38. [PubMed][CrossRef]
67. Long KZ, Rosado JL, Santos JI, Haas M, Al Mamun A, DuPont HL, Nanthakumar NN, Estrada-Garcia T. 2010. Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections. Infect Immun 78:1221–1228. [PubMed][CrossRef]
68. Sarra M, Pallone F, Macdonald TT, Monteleone G. 2010. IL-23/IL-17 axis in IBD. Inflamm Bowel Dis 16:1808–1813. [PubMed][CrossRef]
69. Gonçalves NS, Ghaem-Maghami M, Monteleone G, Frankel G, Dougan G, Lewis DJ, Simmons CP, MacDonald TT. 2001. Critical role for tumour necrosis factor alpha in controlling the number of lumenal pathogenic bacteria and immunopathology in infectious colitis. Infect Immun 69:6651–6659. [PubMed][CrossRef]
70. Ramirez K, Huerta R, Oswald E, Garcia-Tovar C, Hernandez JM, Navarro-Garcia F. 2005. Role of EspA and intimin in expression of proinflammatory cytokines from enterocytes and lymphocytes by rabbit enteropathogenic Escherichia coli-infected rabbits. Infect Immun 73:103–113. [PubMed][CrossRef]
71. Kollias GDouni E, Kassiotis G, Kontoyiannis D. 1999. On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Immunol Rev 169:175–194. [CrossRef]
72. Khan MA, Ma C, Knodler LA, Valdez Y, Rosenberger CM, Deng W, Finlay BB, Vallance BA. 2006. Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice. Infect Immun 74:2522–2536. [PubMed][CrossRef]
73. Hawn TR, Smith KD, Aderem A, Skerrett SJ. 2006. Myeloid differentiation primary response gene (88)- and toll-like receptor 2-deficient mice are susceptible to infection with aerosolized Legionella pneumophila. J Infect Dis 193:1693–1702. [PubMed][CrossRef]
74. Skerrett SJ, Liggitt HD, Hajjar AM, Wilson CB. 2004. Cutting edge: myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus. J Immunol 172:3377–3381. [PubMed][CrossRef]
75. Watson RO, Novik V, Hofreuter D, Lara-Tejero M, Galan JE. 2007. A MyD88-deficient mouse model reveals a role for Nramp1 in Campylobacter jejuni infection. Infect Immun 75:1994–2003. [PubMed][CrossRef]
76. Weiss DS, Takeda K, Akira S, Zychlinsky A, Moreno E. 2005. MyD88, but not Toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus. Infect Immun 73:5137–5143. [PubMed][CrossRef]
77. Akira S, Takeda K. 2004. Toll-like receptor signalling. Nat Rev Immunol 4:499–511. [PubMed][CrossRef]
78. Lebeis SL, Powell KR, Merlin D, Sherman MA, Kalman D. 2009. Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun 77:604–614. [PubMed][CrossRef]
79. Liu Z, Zaki MH, Vogel P, Gurung P, Finlay BB, Deng W, Lamkanfi M, Kanneganti TD. 2012. Role of inflammasomes in host defense against Citrobacter rodentium infection. J Biol Chem 287:16955–16964. [PubMed][CrossRef]
80. Hauf N, Charkraborty T. 2003. Suppression of NF-kappaB activation and proinflammatory cytokine expression by Shiga toxin-producing Escherichia coli. J Immunol 170:2074–2082. [CrossRef]
81. Ruchaud-Sparagano M, Maresca M, Kenny B. 2007. Enteropathogenic Escherichia coli (EPEC) inactivate innate immune responses prior to compromising epithelial barrier function. Cell Microbiol 9:1909–1921. [PubMed][CrossRef]
82. Wong ARC, Pearson JS, Bright MD, Munera D, Robinson KS, Lee SF, Frankel G, Hartland EL. 2011. Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. Mol Microbiol 80:1420–1438. [PubMed][CrossRef]
83. Gao X, Wan F, Mateo K, Callegari E, Wang D, Deng W, Puente J, Li F, Chaussee MS, Finlay BB, Lenardo MJ, Hardwidge PR. 2009. Bacterial effector binding to ribosomal protein S3 subverts NF-κB function. PLoS Pathog 5:1–18. [PubMed][CrossRef]
84. Nadler C, Baruch K, Kobi S, Mills E, Haviv G, Farago M, Alkalay I, Bartfeld S, Meyer T, Ben-Neriah Y, Rosenshine I. 2010. The type III secretion effector NleE inhibits NF-κB activation. PLoS Pathog 6:1–11. [PubMed][CrossRef]
85. Newton HJ, Pearson JS, Badea L, Kelly M, Lucas M, Holloway G, Wagstaff KM, Dunstone MA, Sloan J, Whisstock J, Kaper JB, Robins-Browne RM, Jans DA, Frankel G, Philips AD, Coulson BS, Hartland EL. 2010. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathog 6:1–16. [PubMed][CrossRef]
86. Royan SV, Jones RM, Koutsouris A, Roxas JL, Falzari K, Weflen AW, Kim A, Bellmeyer A, Turner JR, Neish AS, Rhee K-J, Viswanathan VK,. Hecht GA. 2010. Enteropathogenic E. coli non-LEE encoded effectors NleH1 and NleH2 attenuate NF-κB activation. Mol Microbiol 78:1232–1245. [PubMed][CrossRef]
87. Deng W, Puente JL, Gruenheid S, Li Y, Vallance BA, Vazquez A, Barba J, Ibarra JA, O'Donnell P, Metalnikov P, Ashman K, Lee S, Goode D, Pawson T, Finlay BB. 2004. Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proc Natl Acad Sci USA 101:3597–3602. [PubMed][CrossRef]
88. Kelly M, Hart E, Mundy R, Marchès O, Wiles S, Badea L, Luck S, Tauschek M, Frankel G, Robins-Browne RM, Hartland EL. 2006. Essential role of the type III secretion system effector NleB in colonization of mice by Citrobacter rodentium. Infect Immun 74:2328–2337. [PubMed][CrossRef]
89. Iguchi A, Thomson NR, Ogura Y, Saunders D, Ooka T, Henderson IR, Harris D, Asadulghani M, Kurokawa K, Dean P, Kenny B, Quail MA, Thurston S, Dougan G, Hayashi T, Parkhill J, Frankel G. 2009. Complete genome sequence and comparative genome analysis of enteropathogenic Escherichia coli O127:H6 strain E2348/69. J Bacteriol 191:347. [PubMed][CrossRef]
90. Wickham ME, Lupp C, Vazquez A, Marscarenhas M, Coburn B, Coombes BK, Karmali MA, Puente JL, Deng W, Finlay BB. 2007. Citrobacter rodentium virulence in mice associates with bacterial load and the type III effector NleE. Microb Infect 9:400–407. [PubMed][CrossRef]
91. Zurawski DV, Mumy KL, Badea L, Prentice JA, Hartland EL, McCormick BA,. Maurelli AT. 2008. The NleE/OspZ family of effector proteins is required for polymorphonuclear transepithelial migration, a characteristic shared by enteropathogenic Escherichia coli and Shigella flexneri infections. Infect Immun 76:369–379. [PubMed][CrossRef]
92. Bugarel M, Martin A, Fach P, Beutin L. 2011. Virulence gene profiling of enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli strains: a basis for molecular risk assessment of typical and atypical EPEC strains. BMC Microbiol 11:142–152. [PubMed][CrossRef]
93. Buvens G, Piérard D. 2012. Virulence profiling and disease association of verotoxin-producing Escherichia coli O157 and non-O157 isolates in Belgium. Foodborne Path Dis 9:1–6. [PubMed][CrossRef]
94. Vossenkämper A, Marches O, Fairclough PD, Warnes G, Stagg AJ, Lindsay JO, Evans PC, Luong IA, Croft NM, Naik S, Frankel G, MacDonald TT. 2010. Inhibition of NF-κB signaling in human dentritic cells by the enteropathogenic Escherichia coli protein NleE. J Immunol 185:4118–4127. [PubMed][CrossRef]
95. Zhang L, Ding X, Cui J, Xu H, Chen J, Gong Y-N, Hu L, Zhou Y, Ge J, Lu Q, Liu L, Chen S, Shao F. 2011. Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation. Nature 481:204–208. [PubMed][CrossRef]
96. Baruch K, Gur-Arie L, Nadler C, Koby S, Yerushalmi G, Ben-Neriah Y, Yogev O, Shaulian E, Guttman C, Zarivach R, Rosenshine I. 2011. Metalloprotease type III effectors that specifically cleave JNK and NF-κB. EMBO J 30:221–231. [PubMed][CrossRef]
97. Mühlen S, Ruchaud-Sparagano M-H, Kenny B. 2011. Proteasome-independent degradation of canonical NFκB complex components by the NleC protein of pathogenic Escherichia coli. J Biol Chem 286:5100–5107. [PubMed][CrossRef]
98. Pearson JS, Riedmaier P, Marches O, Frankel G, Hartland EL. 2011. A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation. Mol Microbiol 80:219–230. [PubMed][CrossRef]
99. Sham HP, Shames SR, Croxen MA, Ma C, Chan JM, Khan MA, Wickham M, Deng W, Finlay BB, Vallance BA. 2011. Attaching and effacing bacterial effector NleC suppresses epithelial inflammatory responses by inhibiting NF-κB and p38 mitogen-activated protein kinase activation. Infect Immun 79:3552–3562. [PubMed][CrossRef]
100. Perna NT, Plunkett G, Burland V, Mau B, Glasner JD, Rose DJ, Mayhew GF, Evans PS, Gregor J, Kirkpatrick HA, Posfai G, Hackett J, Klink S, Boutin A, Shao Y, Miller L, Grotbeck EJ, Davis NW, Lim A, Dimalanta ET, Potamousis KD, Apodaca J, Anantharaman TSLin J, Yen G, Schwartz DC, Welch RA, Blattner FR. 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409:529–533. [PubMed][CrossRef]
101. Marchès O, Wiles S, Dziva F, La Ragione RM, Schüller S, Best A, Phillips AD, Hartland EL, Woodward MJ, Stevens MP, Frankel G. 2005. Characterization of two non-locus of enterocyte effacement-encoded type III-translocated effectors, NleC and NleD, in attaching and effacing pathogens. Infect Immun 73:8411–8417. [PubMed][CrossRef]
102. Yen H, Ooka T, Iguchi A, Hayashi T, Sugimoto N, Tobe T. 2010. NleC, a type III secretion protease, compromises NF-kappaB activation by targeting p65/RelA. PLoS Pathog 6:e1001231. [PubMed][CrossRef]
103. Jongeneel CV, Bouvier J, Bairoch A. 1989. A unique signature identifies a family of zinc-dependent metallopeptidases. FEBS Lett. 242:211–214. [CrossRef]
104. Gilmore TD, Wolenski FS. 2012. NF-κB: where did it come from and why? Immunol Rev 246:14–35. [PubMed][CrossRef]
105. Hayden MS, Ghosh S. 2008. Shared principles in NF-κB signaling. Cell 132:344–362. [PubMed][CrossRef]
106. Shames SR, Bhavsar AP, Croxen MA, Law RJ, Mak SHC, Deng W, Li Y, Bidshari R, de Hoog CL, Foster LJ, Finlay BB. 2011. The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300. Cell Microbiol 13:1542–1557. [PubMed][CrossRef]
107. Karmali MA, Mascarenhas M, Shen S, Ziebell K, Johnson S, Reid-Smith R, Isaac-Renton J, Clark C, Rahn K, Kaper JB. 2003. Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease. J Clin Microbiol 41:4930–4940. [PubMed][CrossRef]
108. Brown NF, Coombes BK, Bishop JL,. Wickham ME, Lowden MJ, Gal-Mor O, Goode DL, Boyle EC, Sanderson KL, Finlay BB. 2011. Salmonella phage ST64B encodes a member of the SseK/NleB effector family. PLoS One 6:e17824. [PubMed][CrossRef]
109. Gao X, Wang X, Pham TH, Feuerbacher LA, Lubos M-L, Huang M, Olsen R, Mushegian A, Slawson C, Hardwidge PR. 2013. NleB, a bacterial effector with glycosyltransferase activity, targets GADPH function to inhibit NF-κB activation. Cell Host Microb 13:87–99. [PubMed][CrossRef]
110. Wan F, Anderson D, Barnitz R, Snow A, Bidere N, Zheng L, Hegde V, Lam L, Staudt L, Levens D, Deutsch W, Lenardo M. 2007. Ribosomal protein S3: a KH domain subunit in NF-κB complexes that mediates selective gene regulation. Cell 131:927–939. [PubMed][CrossRef]
111. Kim DW, Lenzen G, Page AL, Legrain P, Sansonetti PJ, Parsot C. 2005. The Shigella flexneri effector OspG interferes with innate immune responses by tagretting ubiquitin-conjugating enzymes. Proc Natl Acad Sci USA 102:14046–14051. [PubMed][CrossRef]
112. Wan F, Weaver A, Gao X, Bern M, Hardwidge PR, Lenardo MJ. 2011. IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7. Nat Immunol 12:335–343. [PubMed][CrossRef]
113. Garcia-Angulo VA, Deng W, Thomas NA, Finlay BB, Puente JL. 2008. Regulation of expression and secretion of NleH, a new non-locus of enterocyte effacement-encoded effector in Citrobacter rodentium. J Bacteriol 190:2388–2399. [PubMed][CrossRef]
114. Hemrajani C, Marches O, Wiles S, Girard F, Dennis A, Dziva F, Best A, Phillips AD, Berger CN, Mousnier A, Crepin VF, Kruidenier L, Woodward MJ, Stevens MP, La Ragione RM, MacDonald TT, Frankel G. 2008. Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut. Infect Immun 76:4804–4813. [PubMed][CrossRef]
115. Pham TH, Gao X, Tsai KOlsen R, Wan F, Hardwidge PR. 2012. Functional differences and interactiions between the E. coli type III secretion system effectors NleH1 and NleH2. Infect Immun 80:2133–2140. [PubMed][CrossRef]
116. Mundy R, Girard F, FitzGerald AJ, Frankel G. 2006. Comparison of colonization dynamics and pathology of mice infected with enteropathogenic Escherichia coli, enterohaemorrhagic E. coli and Citrobacter rodentium. FEMS Microbiol Lett 265:126–32. [PubMed][CrossRef]
117. Hemrajani C, Berger CN, Robinson KS, Marchès O, Mousnier A, Frankel G. 2010. NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection. Proc Natl Acad Sci USA 107:3129–3134. [PubMed][CrossRef]
118. Ruchaud-Sparagano M-H, Mühlen S, Dean P, Kenny B. 2011. The enteropathogenic E. coli (EPEC) Tir effector inhibits NF-κB activity by targeting TNFα receptor-associated factors. PLoS Pathog 7:1–14. [PubMed][CrossRef]
119. Yan D, Wang X, Luo L, Cao X, Ge B. 2012. Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs. Nat Immunol 13:1063–1071. [PubMed][CrossRef]
120. Barrow AD, Trowsdale J. 2006. You say ITAM and I say ITIM, let's call the whole thing off: the ambiguity of immunoreceptor signaling. Eur J Immunol 36:1646–1653. [PubMed][CrossRef]
121. Daeron M, Jaeger S, Du Pasquier L, Vivier E. 2008. Immunoreceptor tyrosine-based inhibition motifs: a quest in the past and future. Immunol Rev 224:11–43. [PubMed][CrossRef]
122. Nandan D, Lo R, Reiner NE. 1999. Activation of phosphotyrosine phosphatase activity attenuates mitogen-activated protein kinase signaling and inhibits c-FOS and nitric oxide synthase expression in macrophages infected with Leishmania donovani. Infect Immun 67:4055–4063. [PubMed]
123. Raymond B, Crepin VF, Collins JW, Frankel G. 2011. The WxxxE effector EspT triggers expression of immune mediators in an Erk/JNK and NF-kappaB-dependent manner. Cell Microbiol 13:1881–1893. [PubMed][CrossRef]
124. Keestra AM, Winter MG, Auburger JJ, Frassle SP, Xavier MN, Winter SE, Kim A, Poon V, Ravesloot MM, Waldenmaier JF, Tsolis RM, Eigenheer RA,. Baumler AJ. 2013. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature 496:233–237. [PubMed][CrossRef]
125. Lathem WW, Grys TE, Witowski SE, Torres AG, Kaper JB, Tarr PI, Welch RA. 2002. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves Cl esterase inhibitor. Mol Microbiol. 45:277–288. [PubMed][CrossRef]
126. Hermiston ML, Xu Z, Weiss A. 2003. CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 21:107–137. [PubMed][CrossRef]
127. Ostberg J., Barth RK, Frelinger JG. 1998. The Roman god Janus: a paradigm for the function of CD43. Immunol Today 19:546–550. [PubMed][CrossRef]
128. Szabady RL, Lokuta MA, Walters KB, Huttenlocher A, Welch RA. 2009. Modulation of neutrophil function by a secreted mucinase of Escherichia coli O157:H7. PLoS Pathog 5:e1000320. [PubMed][CrossRef]
129. Forsyth KD, Simpson AC, Fitzpatrick MM, Barratt TM, Levinsky RJ. 1989. Neutrophil-mediated endothelial injury in haemolytic uremic syndrome. Lancet 2:411–414. [PubMed][CrossRef]
microbiolspec.EHEC-0012-2013.citations
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/content/journal/microbiolspec/10.1128/microbiolspec.EHEC-0012-2013
2014-08-15
2017-11-23

Abstract:

The inflammatory response is an integral part of host defense against enterohemorrhagic (EHEC) infection and also contributes to disease pathology. In this article we explore the factors leading to inflammation during EHEC infection and the mechanisms EHEC and other attaching and effacing (A/E) pathogens have evolved to suppress inflammatory signaling. EHEC stimulates an inflammatory response in the intestine through host recognition of bacterial components such as flagellin and lipopolysaccharide. In addition, the activity of Shiga toxin and some type III secretion system effectors leads to increased tissue inflammation. Various infection models of EHEC and other A/E pathogens have revealed many of the immune factors that mediate this response. In particular, the outcome of infection is greatly influenced by the ability of an infected epithelial cell to mount an effective host inflammatory response. The inflammatory response of infected enterocytes is counterbalanced by the activity of type III secretion system effectors such as NleE and NleC that modify and inhibit components of the signaling pathways that lead to proinflammatory cytokine production. Overall, A/E pathogens have taught us that innate mucosal immune responses in the gastrointestinal tract during infection with A/E pathogens are highly complex and ultimate clearance of the pathogen depends on multiple factors, including inflammatory mediators, bacterial burden, and the function and integrity of resident intestinal epithelial cells.

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FIGURE 1

Inflammatory signaling pathways stimulated and inhibited by EHEC. EHEC products such as flagellin and LPS stimulate TLR signaling and the production of cytokines by epithelial cells during infection. At the same time, T3SS effector proteins injected by the LEE-encoded translocon inhibit inflammatory signaling at different points in the various pathways. The signaling factors and T3SS effector proteins, and their mechanisms of action, are described in detail in the main text. TGN, trans-Golgi network; ER, endoplasmic reticulum; Ub, ubiquitin; P, phosphorylation. doi:10.1128/microbiolspec.EHEC-0012-2013.f1

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.EHEC-0012-2013
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