Skip to main content

Advertisement

SpringerLink
Log in

Oral Vaccination Against Helicobacter pyloriInfection Is Not Effective in Mice With Fas Ligand Deficiency

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The aim of this study was to delineate the role of the Fas pathway in vaccination against Helicobacter pylori. C57BL/6 and Fas ligand–deficient (gld) mice were divided into 3 groups: control, H. pyloriinfected, and orally vaccinated (H. pyloriwhole cell sonicate and cholera toxin adjuvant). Oral vaccination prevented H. pyloricolonization in 78% of C57BL/6 mice compared to only 18% of gldmice. Vaccination did not alter the degree of apoptosis in either strain of mice. Vaccination led to significant increase in interleukin (IL)-5 and IL-10 in C57BL/6 but not gldmice. H. pyloriinfection increased interferon (IFN)-γ levels in C57BL/6 but not in gldmice while vaccination had no effect on IFN-γ levels in either strain. Oral vaccination is not effective in Fas ligand–deficient mice likely owing to lack of effective cytokine responses. This indicates that the Fas pathway plays a critical role in promoting an appropriate effector response following H. pylorivaccination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Suerbaum S, Michetti P: Helicobacter pylori infection. N Engl J Med 347:1175–1186, 2002

    Article  CAS  PubMed  Google Scholar 

  2. Shirin H, Moss SF: Helicobacter pylori induced apoptosis. Gut 43:592–594, 1998

    Article  CAS  PubMed  Google Scholar 

  3. Goh KL: Update on the management of Helicobacter pylori infection, including drug-resistant organisms. J Gastroenterol Hepatol 17:482–487, 2002

    Article  CAS  PubMed  Google Scholar 

  4. Lembo A, Caradonna L, Magrone T, et al.: Helicobacter pylori infection, immune response and vaccination. Curr Drug Targets Immune Endocr Metabol Disord 1:199–208, 2001

    CAS  PubMed  Google Scholar 

  5. Kusters JG: Recent developments in Helicobacter pylori vaccination. Scand J Gastroenterol Suppl:15–21, 2001

  6. Ruggiero P, Peppoloni S, Rappuoli R, Del Giudice G: The quest for a vaccine against Helicobacter pylori: How to move from mouse to man? Microbes Infect 5:749–756, 2003

    Article  CAS  PubMed  Google Scholar 

  7. Saldinger PF, Porta N, Launois P, et al.: Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection. Gastroenterology 115:891–897, 1998

    Article  CAS  PubMed  Google Scholar 

  8. Hatzifoti C, Wren BW, Morrow WJ: Helicobacter pylori vaccine strategies#x2013;-triggering a gut reaction. Immunol Today 21:615–619, 2000

    CAS  PubMed  Google Scholar 

  9. Garhart CA, Nedrud JG, Heinzel FP, Sigmund NE, Czinn SJ: Vaccine-induced protection against Helicobacter pylori in mice lacking both antibodies and interleukin-4. Infect Immun 71:3628–633, 2003

    CAS  PubMed  Google Scholar 

  10. Akhiani AA, Pappo J, Kabok Z, et al.: Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells. J Immunol 169:6977–6984, 2002

    CAS  PubMed  Google Scholar 

  11. Akhiani AA, Schon K, Lycke N: Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice. J Immunol 173:3348x2013;3356, 2004

    CAS  PubMed  Google Scholar 

  12. Ashkenazi A, Dixit VM: Death receptors: Signaling and modulation. Science 281:1305–, 1998

    Article  CAS  PubMed  Google Scholar 

  13. Wajant H: The Fas signaling pathway: More than a paradigm. Science 296:1635–1636, 2002

    Article  CAS  PubMed  Google Scholar 

  14. Nagata S, Suda T: Fas and Fas ligand: lpr and gld mutations. Immunol Today 16:39–43, 1995

    Article  CAS  PubMed  Google Scholar 

  15. Matiba B, Mariani SM, Krammer PH: The CD95 system and the death of a lymphocyte. Semin Immunol 9:59–13;68, 1997

    Article  CAS  PubMed  Google Scholar 

  16. Takahashi T, Tanaka M, Brannan CI, et al.: Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76:969–976, 1994

    Article  CAS  PubMed  Google Scholar 

  17. Houghton JM, Bloch LM, Goldstein M, Von Hagen S, Korah RM: In vivo disruption of the fas pathway abrogates gastric growth alterations secondary to Helicobacter infection. J Infect Dis 182:856–864, 2000

    Article  CAS  PubMed  Google Scholar 

  18. Jones NL, Day AS, Jennings H, Shannon PT, Galindo-Mata E, Sherman PM: Enhanced disease severity in Helicobacter pylori-infected mice deficient in Fas signaling. Infect Immun 70:2591–2597, 2002

    CAS  PubMed  Google Scholar 

  19. Lee A, O'Rourke J, De Ungria MC, Robertson B, Daskalopoulos G, Dixon MF: A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain. Gastroenterology 112:1386–1397, 1997

    Article  CAS  PubMed  Google Scholar 

  20. Jones NL, Day AS, Jennings HA, Sherman PM: Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect Immun 67:4237–4242, 1999

    CAS  PubMed  Google Scholar 

  21. Jones NL, Shannon PT, Cutz E, Yeger H, Sherman PM: Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection. Am J Pathol 151:1695–1703, 1997

    CAS  PubMed  Google Scholar 

  22. Sutton P, Danon SJ, Walker M, et al.: Post-immunisation gastritis and Helicobacter infection in the mouse: A long term study. Gut 49:467–473, 2001

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Brooks EG, Bamford KB, Denning TL, Pappo J, Ernst PB: Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion. J Immunol 167:926–934, 2001

    CAS  PubMed  Google Scholar 

  24. Eaton KA, Krakowka S: Chronic active gastritis due to Helicobacter pylori in immunized gnotobiotic piglets. Gastroenterology 103:1580–1586, 1992

    CAS  PubMed  Google Scholar 

  25. Raghavan S, Svennerholm AM, Holmgren J: Effects of oral vaccination and immunomodulation by cholera toxin on experimental Helicobacter pylori infection, reinfection, and gastritis. Infect Immun 70:4621–2002

    CAS  PubMed  Google Scholar 

  26. Garhart CA, Redline RW, Nedrud JG, Czinn SJ: Clearance of Helicobacter pylori Infection and resolution of postimmunization gastritis in a kinetic study of prophylactically immunized mice. Infect Immun 70:3529–3538, 2002

    Article  CAS  PubMed  Google Scholar 

  27. Menaker RJ, Jones NL: Fascination with bacteria-triggered cell death: The significance of Fas-mediated apoptosis during bacterial infection in vivo. Microbes Infect 5:1149–1158, 2003

    Article  CAS  PubMed  Google Scholar 

  28. Kohda K, Tanaka K, Aiba Y, Yasuda M, Miwa T, Koga Y: Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer. Gut 44:456–462, 1999

    Article  CAS  PubMed  Google Scholar 

  29. Scotiniotis IA, Rokkas T, Furth EE, Rigas B, Shiff SJ: Altered gastric epithelial cell kinetics in Helicobacter pylori-associated intestinal metaplasia: Implications for gastric carcinogenesis. Int J Cancer 85:192–200, 2000

    CAS  PubMed  Google Scholar 

  30. Mohammadi M, Nedrud J, Redline R, Lycke N, Czinn SJ: Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load. Gastroenterology 113:1848–1857, 1997

    Article  CAS  PubMed  Google Scholar 

  31. Cohen PL, Eisenberg RA: Lpr and gld: Single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269, 1991

    Article  CAS  PubMed  Google Scholar 

  32. Giese T, Davidson WF: Chronic treatment of C3H-lpr/lpr and C3H-gld/gld mice with anti-CD8 monoclonal antibody prevents the accumulation of double negative T cells but not autoantibody production. J Immunol 152:2000–2010, 1994

    CAS  PubMed  Google Scholar 

  33. Giese T, Davidson WF: The accumulation of B220+ CD4Ȓ CD8Ȓ (DN) T cells in C3H-lpr/lpr mice is not accelerated by the stimulation of CD8+ T cells or B220+ DN T cells with staphylococcal enterotoxin B and occurs independently of V beta 8+ T cells. Int Immunol 7:1213–1223, 1995

    CAS  PubMed  Google Scholar 

  34. Giese T, Davidson WF: In CD8+ T cell-deficient lpr/lpr mice, CD4+ B220+ and CD4+ B220-T cells replace B220+ double-negative T cells as the predominant populations in enlarged lymph nodes. J Immunol 154:4986–4995, 1995

    CAS  PubMed  Google Scholar 

  35. Ford MS, Young KJ, Zhang Z, Ohashi PS, Zhang L: The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo. J Exp Med 196:261–67, 2002

    Article  CAS  PubMed  Google Scholar 

  36. Hamad AR, Mohamood AS, Trujillo CJ, Huang CT, Yuan E, Schneck JP: B220+ double-negative T cells suppress polyclonal T cell activation by a Fas-independent mechanism that involves inhibition of IL-2 production. J Immunol 171:2421–2426, 2003

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Yaron Avitzur MD, Esther Galindo-Mata & Nicola L. Jones MD, PhD, FRCPC

  2. Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada

    Yaron Avitzur MD & Nicola L. Jones MD, PhD, FRCPC

  3. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    Nicola L. Jones MD, PhD, FRCPC

  4. Division of Gastroenterology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada

    Nicola L. Jones MD, PhD, FRCPC

Authors
  1. Yaron Avitzur MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esther Galindo-Mata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicola L. Jones MD, PhD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola L. Jones MD, PhD, FRCPC.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avitzur, Y., Galindo-Mata, E. & Jones, N.L. Oral Vaccination Against Helicobacter pyloriInfection Is Not Effective in Mice With Fas Ligand Deficiency. Dig Dis Sci 50, 2300–2306 (2005). https://doi.org/10.1007/s10620-005-3051-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-005-3051-5

KeyWords

Search

Navigation