Reprint requests to: John Y. Kao, Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 6520A Medical Science Research Building 1, Special Postal Code 5682, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109, USA. Tel.: (734) 647-2964; Fax: (734) 763-2535; E-mail: [email protected]

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Abstract

Background: The growing concern over the emergence of antibiotic-resistant Helicobacter pylori infection is propelling the development of an efficacious vaccine to control this highly adaptive organism.

Aim: We studied the use of a dendritic cell (DC)-based vaccine against H. pylori infection in mice.

Methods: The cellular immune responses to murine bone marrow-derived DCs pulsed with phosphate-buffered saline (PBS-DC) or live H. pylori SS1 (HP-DC) were assessed in vitro and in vivo. The protective immunity against H. pylori SS1 oral challenge was compared between HP-DC or PBS-DC immunized mice. The effect of regulatory T-cell (Treg) depletion by anti-CD25 antibody on HP-DC vaccine efficacy was also evaluated.

Results: HP-DC induced a Th1-dominant response in vitro. In vivo, HP-DC immunized mice were characterized by a mixed Th1/Th2 peripheral immune response. However, in the stomach, HP-DC immunized mice expressed a higher level of IFN-γ compared to PBS-DC immunized mice; no difference was found for interleukin-5 expressions in the stomach. A lower bacterial colonization post-H. pylori challenge was observed in HP-DC immunized mice compared to PBS-DC immunized mice with no significant difference in gastritis severity. H. pylori-specific Th1 response and protective immunity were further enhanced in vivo by depletion of Treg with anti-CD25 antibody.

Conclusion: DC-based anti-H. pylori vaccine induced H. pylori-specific helper T-cell responses capable of limiting bacterial colonization. Our data support the critical role of effector cellular immune response in the development of H. pylori vaccine.

References

1 Fujioka T, Yoshiiwa A, Okimoto T, Kodama M, Murakami K. Guidelines for the management of Helicobacter pylori infection in Japan: Current status and future prospects. J Gastroenterol 2007; 42 (Suppl.): 3–6.
10.1007/s00535-006-1938-3
PubMed Web of Science® Google Scholar
2 Raymond J, Burucoa C, Pietrini O, et al. Clarithromycin resistance in Helicobacter pylori strains isolated from French children: Prevalence of the different mutations and coexistence of clones harboring two different mutations in the same biopsy. Helicobacter 2007; 12: 157–63.
10.1111/j.1523-5378.2007.00486.x
CAS PubMed Web of Science® Google Scholar
3 Hu CT, Wu CC, Lin CY, et al. Resistance rate to antibiotics of Helicobacter pylori isolates in eastern Taiwan. J Gastroenterol Hepatol 2007; 22: 720–3.
10.1111/j.1440-1746.2006.04743.x
CAS PubMed Web of Science® Google Scholar
4 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 2002; 169: 6977–84.
10.4049/jimmunol.169.12.6977
CAS PubMed Web of Science® Google Scholar
5 Garhart CA, Heinzel FP, Czinn SJ, Nedrud JG. Vaccine-induced reduction of Helicobacter pylori colonization in mice is interleukin-12 dependent but gamma interferon and inducible nitric oxide synthase independent. Infect Immun 2003; 71: 910–21.
10.1128/IAI.71.2.910-921.2003
CAS PubMed Web of Science® Google Scholar
6 Kao JY, Rathinavelu S, Eaton KA, et al. Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: A mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol 2006; 291: G73–81.
10.1152/ajpgi.00139.2005
CAS PubMed Web of Science® Google Scholar
7 Kao JY, Zhang M, Chen CM, Pierzchala A, Chen JJ. Aberrant T helper cell response in tumor-bearing mice limits the efficacy of dendritic cell vaccine. Immunol Lett 2006; 105: 16–25.
10.1016/j.imlet.2005.11.026
CAS PubMed Web of Science® Google Scholar
8 Permin H, Andersen LP. Inflammation, immunity, and vaccines for Helicobacter infection. Helicobacter 2005; 10: 21–5.
10.1111/j.1523-5378.2005.00337.x
CAS PubMed Web of Science® Google Scholar
9 Hoffelner H, Rieder G, Haas R. Helicobacter pylori vaccine development: Optimisation of strategies and importance of challenging strain and animal model. Int J Med Microbiol 2007.
Google Scholar
10 Saito H, Frleta D, Dubsky P, Palucka AK. Dendritic cell-based vaccination against cancer. Hematol Oncol Clin North Am 2006; 20: 689–710.
10.1016/j.hoc.2006.02.011
PubMed Web of Science® Google Scholar
11 Zavros Y, Rathinavelu S, Kao JY, et al. Treatment of helicobacter gastritis with IL-4 requires somatostatin. Proc Natl Acad Sci USA 2003; 100: 12944–9.
10.1073/pnas.2135193100
CAS PubMed Web of Science® Google Scholar
12 Kao JY, Gong Y, Chen CM, Zheng QD, Chen JJ. Tumor-derived TGF-beta reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol 2003; 170: 3806–11.
10.4049/jimmunol.170.7.3806
CAS PubMed Web of Science® Google Scholar
13 Eaton KA, Logan SM, Baker PE, Peterson RA, Monteiro MA, Altman E. Helicobacter pylori with a truncated lipopolysaccharide O chain fails to induce gastritis in SCID mice injected with splenocytes from wild-type C57BL/6J mice. Infect Immun 2004; 72: 3925–31.
10.1128/IAI.72.7.3925-3931.2004
CAS PubMed Web of Science® Google Scholar
14 Eaton KA, Mefford M, Thevenot T. The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice. J Immunol 2001; 166: 7456–61.
10.4049/jimmunol.166.12.7456
CAS PubMed Web of Science® Google Scholar
15 Fox JG, Dewhirst FE, Shen Z, et al. Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis. Gastroenterology 1998; 114: 755–63.
10.1016/S0016-5085(98)70589-X
CAS PubMed Web of Science® Google Scholar
16 Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy. Nat Med 2000; 6: 536–42.
10.1038/75015
CAS PubMed Web of Science® Google Scholar
17 Hafsi N, Voland P, Schwendy S, et al. Human dendritic cells respond to Helicobacter pylori, promoting NK cell and Th1-effector responses in vitro. J Immunol 2004; 173: 1249–57.
10.4049/jimmunol.173.2.1249
CAS PubMed Web of Science® Google Scholar
18 Guiney DG, Hasegawa P, Cole SP. Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect Immun 2003; 71: 4163–6.
10.1128/IAI.71.7.4163-4166.2003
CAS PubMed Web of Science® Google Scholar
19 Fischbach W, Goebeler-Kolve M, Ruskone-Fourmestraux A, et al. Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be safely managed by a watch-and-wait strategy. Experience from a large international series. Gut 2007.
Google Scholar
20 Otsu S, Gotoh K, Yamashiro T, et al. Transfer of antigen-pulsed dendritic cells induces specific T-cell proliferation and a therapeutic effect against long-term Helicobacter pylori infection in mice. Infect Immun 2006; 74: 984–93.
10.1128/IAI.74.2.984-993.2006
CAS PubMed Web of Science® Google Scholar
21 Sutton P, Wilson J, Kosaka T, Wolowczuk I, Lee A. Therapeutic immunization against Helicobacter pylori infection in the absence of antibodies. Immunol Cell Biol 2000; 78: 28–30.
10.1046/j.1440-1711.2000.00881.x
CAS PubMed Web of Science® Google Scholar
22 Blanchard TG, Czinn SJ, Redline RW, Sigmund N, Harriman G, Nedrud JG. Antibody-independent protective mucosal immunity to gastric Helicobacter infection in mice. Cell Immunol 1999; 191: 74–80.
10.1006/cimm.1998.1421
CAS PubMed Web of Science® Google Scholar
23 Rad R, Brenner L, Bauer S, et al. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology 2006; 131: 525–37.
10.1053/j.gastro.2006.05.001
CAS PubMed Web of Science® Google Scholar

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Volume13, Issue3

June 2008

Pages 200-208

Helicobacter pylori-Pulsed Dendritic Cells Induce H. pylori-Specific Immunity in Mice

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Helicobacter pylori-Pulsed Dendritic Cells Induce H. pylori-Specific Immunity in Mice

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