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Journal of Immunology Research
Volume 2015, Article ID 981328, 10 pages
http://dx.doi.org/10.1155/2015/981328
Review Article

Helicobacter pylori and T Helper Cells: Mechanisms of Immune Escape and Tolerance

Department of Health Science, University of Catanzaro “Magna Graecia”, 88100 Catanzaro, Italy

Received 4 December 2014; Accepted 29 January 2015

Academic Editor: Muhammad Atif Zahoor

Copyright © 2015 Tiziana Larussa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Höcker and P. Hohenberger, “Helicobacter pylori virulence factors-one part of a big picture,” The Lancet, vol. 362, no. 9391, pp. 1231–1233, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Amedei, C. Della Bella, E. Silvestri, D. Prisco, and M. M. D'Elios, “T cells in gastric cancer: friends or foes,” Clinical and Developmental Immunology, vol. 2012, Article ID 690571, 10 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. L. Cellini, “Helicobacter pylori: a chameleon-like approach to life,” World Journal of Gastroenterology, vol. 20, no. 19, pp. 5575–5582, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. H. M. Algood and T. L. Cover, “Helicobacter pylori persistence: an overview of interactions between H. pylori and host immune defenses,” Clinical Microbiology Reviews, vol. 19, no. 4, pp. 597–613, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Hitzler, E. Kohler, D. B. Engler, A. S. Yazgan, and A. Müller, “The role of Th cell subsets in the control of helicobacter infections and in T cell-driven gastric immunopathology,” Frontiers in Immunology, vol. 3, article 142, Article ID Article 142, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. L. E. Harrington, R. D. Hatton, P. R. Mangan et al., “Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages,” Nature Immunology, vol. 6, no. 11, pp. 1123–1132, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Sakaguchi, M. Miyara, C. M. Costantino, and D. A. Hafler, “FOXP3+ regulatory T cells in the human immune system,” Nature Reviews Immunology, vol. 10, no. 7, pp. 490–500, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Zhang, N. Yamada, Y.-L. Wu, M. Wen, T. Matsuhisa, and N. Matsukura, “Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients,” World Journal of Gastroenterology, vol. 11, no. 7, pp. 976–981, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. K. T. Wilson and J. E. Crabtree, “Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies,” Gastroenterology, vol. 133, no. 1, pp. 288–308, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Meyer, K. T. Wilson, and S. P. James, “Modulation of innate cytokine responses by products of Helicobacter pylori,” Infection and Immunity, vol. 68, no. 11, pp. 6265–6272, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. L. S. Berenson, N. Ota, and K. M. Murphy, “Issues in T-helper 1 development—resolved and unresolved,” Immunological Reviews, vol. 202, no. 1, pp. 157–174, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. K. A. Eaton, L. H. Benson, J. Haeger, and B. M. Gray, “Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice,” Infection and Immunity, vol. 74, no. 8, pp. 4673–4684, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Mohammadi, J. Nedrud, R. Redline, N. Lycke, and S. J. Czinn, “Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load,” Gastroenterology, vol. 113, no. 6, pp. 1848–1857, 1997. View at Publisher · View at Google Scholar · View at Scopus
  14. P. F. Saldinger, N. Porta, P. Launois et al., “Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection,” Gastroenterology, vol. 115, no. 4, pp. 891–897, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. C. A. Garhart, J. G. Nedrud, F. P. Heinzel, N. E. Sigmund, and S. J. Czinn, “Vaccine-induced protection against Helicobacter pylori in mice lacking both antibodies and interleukin-4,” Infection and Immunity, vol. 71, no. 6, pp. 3628–3633, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. B. M. Gray, C. A. Fontaine, S. A. Poe, and K. A. Eaton, “Complex T cell interactions contribute to Helicobacter pylori gastritis in mice,” Infection and Immunity, vol. 81, no. 3, pp. 740–752, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. F. Luzza, T. Parrello, G. Monteleone et al., “Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa,” The Journal of Immunology, vol. 165, no. 9, pp. 5332–5337, 2000. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Lundgren, E. Strömberg, Å. Sjöling et al., “Mucosal FOXP3-expressing CD4+CD25high regulatory T cells in Helicobacter pylori-infected patients,” Infection and Immunity, vol. 73, no. 1, pp. 523–531, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Raghavan and M. Quiding-Järbrink, “Immune modulation by regulatory T cells in Helicobacter pylori-associated diseases,” Endocrine, Metabolic and Immune Disorders—Drug Targets, vol. 12, no. 1, pp. 71–85, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. M. García, B. Bellosillo, B. Sánchez-González et al., “Study of regulatory T-cells in patients with gastric malt lymphoma: influence on treatment response and outcome,” PLoS ONE, vol. 7, no. 12, Article ID e51681, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. P. McGuirk, C. McCann, and K. H. Mills, “Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis,” The Journal of Experimental Medicine, vol. 195, no. 2, pp. 221–231, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Belkaid, C. A. Piccirillo, S. Mendez, E. M. Shevach, and D. L. Sacks, “CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity,” Nature, vol. 420, no. 6915, pp. 502–507, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. S. Raghavan, M. Fredriksson, A. M. Svennerholm, J. Holmgren, and E. Suri-Payer, “Absence of CD4+Cd25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori-infected mice,” Clinical & Experimental Immunology, vol. 132, no. 3, pp. 393–400, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Kaparakis, K. L. Laurie, O. Wijburg et al., “CD4+ CD25+ regulatory T cells modulate the T-cell and antibody responses in Helicobacter-Infected BALB/c mice,” Infection and Immunity, vol. 74, no. 6, pp. 3519–3529, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Mohammadi, S. Czinn, R. Redline, and J. Nedrud, “Helicobacter-specific cell-mediated immune responses display a predominant Th1 phenotype and promote a delayed-type hypersensitivity response in the stomachs of mice,” The Journal of Immunology, vol. 156, no. 12, pp. 4729–4738, 1996. View at Google Scholar · View at Scopus
  26. M. M. D'Elios, M. Manghetti, M. de Carli et al., “T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease,” Journal of Immunology, vol. 158, no. 2, pp. 962–967, 1997. View at Google Scholar · View at Scopus
  27. K. A. Eaton, M. Mefford, and T. Thevenot, “The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice,” Journal of Immunology, vol. 166, no. 12, pp. 7456–7461, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Gebert, W. Fischer, E. Weiss, R. Hoffmann, and R. Haas, “Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation,” Science, vol. 301, no. 5636, pp. 1099–1102, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. M. S. Sundrud, V. J. Torres, D. Unutmaz, and T. L. Cover, “Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 20, pp. 7727–7732, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Gerhard, C. Schmees, P. Voland et al., “A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells,” Gastroenterology, vol. 128, no. 5, pp. 1327–1339, 2005. View at Google Scholar · View at Scopus
  31. C. Schmees, C. Prinz, T. Treptau et al., “Inhibition of T-cell proliferation by Helicobacter pyloriγ-glutamyl transpeptidase,” Gastroenterology, vol. 132, no. 5, pp. 1820–1833, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Zabaleta, D. J. McGee, A. H. Zea et al., “Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta),” Journal of Immunology, vol. 173, no. 1, pp. 586–593, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Wang, E. G. Brooks, K. B. Bamford, T. L. Denning, J. Pappo, and P. B. Ernst, “Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion,” Journal of Immunology, vol. 167, no. 2, pp. 926–934, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Meyer, K. S. Ramanujam, A. P. Gobert, S. P. James, and K. T. Wilson, “Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori,” The Journal of Immunology, vol. 171, no. 8, pp. 3913–3917, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Pellicanò, M. Imeneo, I. Leone, T. Larussa, and F. Luzza, “Enhanced activation of cyclooxygenase-2 downregulates Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa,” Helicobacter, vol. 12, no. 3, pp. 193–199, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Larussa, I. Leone, E. Suraci et al., “Enhanced expression of indoleamine 2,3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production,” Helicobacter, vol. 20, no. 1, pp. 41–48, 2015. View at Publisher · View at Google Scholar
  37. D. Bimczok, J. M. Grams, R. D. Stahl, K. B. Waites, L. E. Smythies, and P. D. Smith, “Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori,” Gastroenterology, vol. 141, no. 3, pp. 929–938, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. M. P. Bergman, A. Engering, H. H. Smits et al., “Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN,” The Journal of Experimental Medicine, vol. 200, no. 8, pp. 979–990, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. I. M. Toller, I. Hitzler, A. Sayi, and A. Mueller, “Prostaglandin E2 prevents Helicobacter-induced gastric preneoplasia and facilitates persistent infection in a mouse model,” Gastroenterology, vol. 138, no. 4, pp. 1455.e4–1467.e4, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. W. Ouyang, J. K. Kolls, and Y. Zheng, “The biological functions of T helper 17 cell effector cytokines in inflammation,” Immunity, vol. 28, no. 4, pp. 454–467, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Das, G. Suarez, E. J. Beswick, J. C. Sierra, D. Y. Graham, and V. E. Reyes, “Expression of B7-H1 on gastric epithelial cells: Its potential role in regulating T cells during Helicobacter pylori infection,” Journal of Immunology, vol. 176, no. 5, pp. 3000–3009, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. T. T. Lina, I. V. Pinchuk, J. House et al., “CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection,” Journal of Immunology, vol. 191, no. 7, pp. 3838–3846, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Y. Kao, M. Zhang, M. J. Miller et al., “Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice,” Gastroenterology, vol. 138, no. 3, pp. 1046–1054, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Oertli, M. Sundquist, I. Hitzler et al., “DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection,” The Journal of Clinical Investigation, vol. 122, no. 3, pp. 1082–1096, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Oertli and A. Müller, “Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma,” Gut Microbes, vol. 3, no. 6, pp. 566–571, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. K. J. Maloy, L. Salaun, R. Cahill, G. Dougan, N. J. Saunders, and F. Powrie, “CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms,” Journal of Experimental Medicine, vol. 197, no. 1, pp. 111–119, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. P. J. Mitchell, B. Afzali, H. Fazekasova et al., “Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1β production by dendritic cells,” Clinical & Experimental Immunology, vol. 170, no. 3, pp. 300–309, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Rowland, L. Daly, M. Vaughan, A. Higgins, B. Bourke, and B. Drumm, “Age-specific incidence of Helicobacter pylori,” Gastroenterology, vol. 130, no. 1, pp. 65–72, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Luzza, E. Suraci, T. Larussa, I. Leone, and M. Imeneo, “High exposure, spontaneous clearance, and low incidence of active Helicobacter pylori infection: the Sorbo San Basile study,” Helicobacter, vol. 19, no. 4, pp. 296–305, 2014. View at Publisher · View at Google Scholar
  50. C. Serrano, S. W. Wright, D. Bimczok et al., “Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children,” Mucosal Immunology, vol. 6, no. 5, pp. 950–959, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Luzza, T. Parrello, L. Sebkova et al., “Expression of proinflammatory and Th1 but not Th2 cytokines is enhanced in gastric mucosa of Helicobacter pylori infected children,” Digestive and Liver Disease, vol. 33, no. 1, pp. 14–20, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. A. I. Lopes, M. Quiding-Jarbrink, A. Palha et al., “Cytokine expression in pediatric Helicobacter pylori infection,” Clinical and Diagnostic Laboratory Immunology, vol. 12, no. 8, pp. 994–1002, 2005. View at Google Scholar · View at Scopus
  53. A. Marchant and M. Goldman, “T cell-mediated immune responses in human newborns: ready to learn?” Clinical and Experimental Immunology, vol. 141, no. 1, pp. 10–18, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. F. Freire de Melo, G. A. Rocha, A. M. Rocha et al., “Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns,” International Journal of Medical Microbiology, vol. 304, no. 3-4, pp. 300–306, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. T. R. Bhuiyan, M. M. Islam, T. Uddin et al., “Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults,” PLoS ONE, vol. 9, no. 4, Article ID e93943, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Bontems, E. Aksoy, A. Burette et al., “NF-κB activation and severity of gastritis in Helicobacter pylori-infected children and adults,” Helicobacter, vol. 19, no. 3, pp. 157–167, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. I. C. Arnold, J. Y. Lee, M. R. Amieva et al., “Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia,” Gastroenterology, vol. 140, no. 1, pp. 199–209, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Y. Cho, M. S. Cho, and J. W. Seo, “FOXP3+ regulatory T cells in children with Helicobacter pylori Infection,” Pediatric and Developmental Pathology, vol. 15, no. 2, pp. 118–126, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. P. R. Harris, S. W. Wright, C. Serrano et al., “Helicobacter pylori gastritis in children is associated with a regulatory T-cell response,” Gastroenterology, vol. 134, no. 2, pp. 491–499, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Freire de Melo, A. M. Rocha, G. A. Rocha et al., “A regulatory instead of an IL-17 T response predominates in Helicobacter pylori-associated gastritis in children,” Microbes and Infection, vol. 14, no. 4, pp. 341–347, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Rad, L. Brenner, S. Bauer et al., “CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo,” Gastroenterology, vol. 131, no. 2, pp. 525–537, 2006. View at Publisher · View at Google Scholar
  62. W. Chen, D. Shu, and V. S. Chadwick, “Helicobacter pylori infection: mechanism of colonization and functional dyspepsia reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10,” Journal of Gastroenterology and Hepatology, vol. 16, no. 4, pp. 377–383, 2001. View at Google Scholar
  63. W. E. Karnes Jr., I. M. Samloff, M. Siurala et al., “Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis,” Gastroenterology, vol. 101, no. 1, pp. 167–174, 1991. View at Google Scholar · View at Scopus
  64. S. Zawahir, S. J. Czinn, J. G. Nedrud, and T. G. Blanchard, “Vaccinating against Helicobacter pylori in the developing world,” Gut Microbes, vol. 4, no. 6, pp. 568–576, 2013. View at Google Scholar · View at Scopus
  65. A. A. Akhiani, J. Pappo, Z. Kabok et al., “Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells,” The Journal of Immunology, vol. 169, no. 12, pp. 6977–6984, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. C. A. Garhart, F. P. Heinzel, S. J. Czinn, and J. G. Nedrud, “Vaccine-induced reduction of Helicobacter pylori colonization in mice is interleukin-12 dependent but gamma interferon and inducible nitric oxide synthase independent,” Infection and Immunity, vol. 71, no. 2, pp. 910–921, 2003. View at Publisher · View at Google Scholar · View at Scopus