Skip to main content

Advertisement

Log in

H.pylori Infection Alleviates Acute and Chronic Colitis with the Expansion of Regulatory B Cells in Mice

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Epidemiological studies showed that there was an inverse relationship between Helicobacter pylori (H. pylori) infection and the incidence of inflammatory bowel diseases (IBD). Our previous research indicated that the regulatory immune responses induced by H. pylori infection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, mice were infected with H. pylori SS1, and then colitis was induced by 3% dextran sulphate sodium (DSS), to investigate the role of the regulatory B cells in the effects of H. pylori infection on acute and chronic colitis. In acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less, the proinflammatory cytokines mRNA expression downregulated in colonic mucosa, and the percentages of CD19+IL-10+Breg cells were higher in the H. pylori/DSS co-treated groups compared with the DSS-treated groups. Our study suggests that H. pylori infection can alleviate the acute and chronic colitis induced by DSS, and CD19+IL-10+Breg cells may play a critical role in the alleviation of acute and chronic colitis following H. pylori infection.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cadamuro, A.C., A.F. Rossi, N.M. Maniezzo, and A.E. Silva. 2014. Helicobacter pylori infection: host immune response, implications on gene expression and microRNAs. World Journal of Gastroenterology 20: 1424–1437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rad, R., L. Brenner, S. Bauer, S. Schwendy, L. Layland, C.P. da Costa, W. Reindl, A. Dossumbekova, M. Friedrich, D. Saur, H. Wagner, R.M. Schmid, and C. Prinz. 2006. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology 131: 525–537.

    Article  CAS  PubMed  Google Scholar 

  3. Kuipers, E.J., and P. Michetti. 2005. Bacteria and mucosal inflammation of the gut: lessons from Helicobacter pylori. Helicobacter 10: 66–70.

    Article  PubMed  Google Scholar 

  4. D'Elios, M.M., and S.J. Czinn. 2014. Immunity, inflammation, and vaccines for Helicobacter pylori. Helicobacter 19 (Suppl 1): 19–26.

    Article  CAS  PubMed  Google Scholar 

  5. Lundgren, A., E. Stromberg, A. Sjoling, C. Lindholm, K. Enarsson, A. Edebo, E. Johnsson, E. Suri-Payer, P. Larsson, A. Rudin, A.M. Svennerholm, and B.S. Lundin. 2005. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infection and Immunity 73: 523–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wei, L., J. Wang, and Y. Liu. 2014. Prior to Foxp3(+) regulatory T-cell induction, interleukin-10-producing B cells expand after Helicobacter pylori infection. Pathogens Disease 72: 45–54.

    Article  CAS  PubMed  Google Scholar 

  7. Kao, J.Y., M. Zhang, M.J. Miller, J.C. Mills, B. Wang, M. Liu, K.A. Eaton, W. Zou, B.E. Berndt, T.S. Cole, T. Takeuchi, S.Y. Owyang, and J. Luther. 2010. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology 138: 1046–1054.

    Article  CAS  PubMed  Google Scholar 

  8. Chang, L.L., S.W. Wang, I.C. Wu, F.J. Yu, Y.C. Su, Y.P. Chen, D.C. Wu, C.H. Kuo, and C.H. Hung. 2012. Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients. Applied Microbiology and Biotechnology 96: 211–220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu, Xiaowei, Hongzan Ji, Miaofang Yang, Lin Wu, and F. Wang. 2015. Helicobacter pylori infection and inflammatory bowel disease in Asians: a meta analysis. World Journal of Gastroenterology 21: 4750–4756.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Luther, J., M. Dave, P.D. Higgins, and J.Y. Kao. 2010. Association between Helicobacter pylori infection and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Inflammatory Bowel Diseases 16: 1077–1084.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Reibman, J., M. Marmor, J. Filner, M.E. Fernandez-Beros, L. Rogers, G.I. Perez-Perez, and M.J. Blaser. 2008. Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One 3: e4060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zevit, Noam, Ran D. Balicer, Herman Avner Cohen, Dorit Karsh, Yaron Niv, and R. Shamir. 2011. Inverse association between Helicobacter pylori and pediatric asthma in a high prevalence population. Helicobacter 17: 30–35.

    Article  Google Scholar 

  13. Herbarth, O., M. Bauer, G.J. Fritz, P. Herbarth, U. Rolle-Kampczyk, P. Krumbiegel, M. Richter, and T. Richter. 2007. Helicobacter pylori colonisation and eczema. Journal of Epidemiology and Community Health 61: 638–640.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dieleman, L.A., M.J. Palmen, H. Akol, E. Bloemena, A.S. Pena, S.G.M. Meuwissen, and E.P.V. Rees. 1998. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clinical and Experimental Immunology 114: 385–391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Eastaff-Leung, N., N. Mabarrack, A. Barbour, A. Cummins, and S. Barry. 2010. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. Journal of Clinical Immunology 30: 80–89.

    Article  CAS  PubMed  Google Scholar 

  16. Higgins, P.D., L.A. Johnson, J. Luther, M. Zhang, K.L. Sauder, L.P. Blanco, and J.Y. Kao. 2011. Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine. Inflammatory Bowel Diseases 17: 1398–1408.

    Article  PubMed  Google Scholar 

  17. Luther, J., S.Y. Owyang, T. Takeuchi, T.S. Cole, M. Zhang, M. Liu, J. Erb-Downward, J.H. Rubenstein, C.C. Chen, A.V. Pierzchala, J.A. Paul, and J.Y. Kao. 2011. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut 60: 1479–1486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gil, J.H., J.W. Seo, M.S. Cho, J.H. Ahn, and H.Y. Sung. 2014. Role of Treg and TH17 cells of the gastric mucosa in children with Helicobacter pylori gastritis. Journal of Pediatric Gastroenterology and Nutrition 58: 245–251.

    Article  CAS  PubMed  Google Scholar 

  19. Lv, Q., S.M. Qiao, Y. Xia, C. Shi, Y.F. Xia, G.X. Chou, Z.T. Wang, Y. Dai, and Z.F. Wei. 2015. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. International Immunopharmacology 29: 787–797.

    Article  CAS  PubMed  Google Scholar 

  20. Ansary, M.M., S. Ishihara, A. Oka, R. Kusunoki, N. Oshima, T. Yuki, K. Kawashima, H. Maegawa, N. Kashiwagi, and Y. Kinoshita. 2014. Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function. Inflammatory Bowel Diseases 20: 2308–2320.

    Article  PubMed  Google Scholar 

  21. Okayasu, Isao, Shigeru Hatakeyama, Masahiro Yamada, Toshifumi Ohkusa, Yoshio Inagaki, and R. Nakaya. 1990. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98: 694–702.

    Article  CAS  Google Scholar 

  22. Sonnenberg, A., and R.M. Genta. 2012. Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 35: 469–476.

    Article  CAS  Google Scholar 

  23. Yanaba, K., A. Yoshizaki, Y. Asano, T. Kadono, T.F. Tedder, and S. Sato. 2011. IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model. The American Journal of Pathology 178: 735–743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Oka, A., S. Ishihara, Y. Mishima, Y. Tada, R. Kusunoki, N. Fukuba, T. Yuki, K. Kawashima, S. Matsumoto, and Y. Kinoshita. 2014. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease. Inflammatory Bowel Diseases 20: 315–328.

    Article  PubMed  Google Scholar 

  25. Sattler, S., G.S. Ling, D. Xu, L. Hussaarts, A. Romaine, H. Zhao, L. Fossati-Jimack, T. Malik, H.T. Cook, M. Botto, Y.L. Lau, H.H. Smits, F.Y. Liew, and F.P. Huang. 2014. IL-10-producing regulatory B cells induced by IL-33 (Breg (IL-33)) effectively attenuate mucosal inflammatory responses in the gut. Journal of Autoimmunity 50: 107–122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yanaba, K., J.D. Bouaziz, K.M. Haas, J.C. Poe, M. Fujimoto, and T.F. Tedder. 2008. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28: 639–650.

    Article  CAS  PubMed  Google Scholar 

  27. Rosser, E.C., and C. Mauri. 2015. Regulatory B cells: origin, phenotype, and function. Immunity 42: 607–612.

    Article  CAS  PubMed  Google Scholar 

  28. Lu, F.T., W. Yang, Y.H. Wang, H.D. Ma, W. Tang, J.B. Yang, L. Li, A.A. Ansari, and Z.X. Lian. 2015. Thymic B cells promote thymus-derived regulatory T cell development and proliferation. Journal of Autoimmunity 61: 62–72.

    Article  CAS  PubMed  Google Scholar 

  29. Ding, Y., Y. Liang, B. Deng, A. Qiao, K. Wu, W. Xiao, and W. Gong. 2014. Induction of TGF-beta and IL-10 production in dendritic cells using astilbin to inhibit dextran sulfate sodium-induced colitis. Biochemical and Biophysical Research Communications 446: 529–534.

    Article  CAS  PubMed  Google Scholar 

  30. Reyes, J.L., A. Wang, M.R. Fernando, R. Graepel, G. Leung, N. van Rooijen, M. Sigvardsson, and D.M. McKay. 2015. Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages. Journal of Immunology 194: 364–378.

    Article  CAS  Google Scholar 

  31. Nagai, S., H. Mimuro, T. Yamada, Y. Baba, K. Moro, T. Nochi, H. Kiyono, T. Suzuki, C. Sasakawa, and S. Koyasu. 2007. Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis. Proceedings of the National Academy of Sciences of the United States of America 104: 8971–8976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Watanabe, N., K. Kiriya, and T. Chiba. 2008. Small intestine Peyer's patches are major induction sites of the Helicobacter-induced host immune responses. Gastroenterology 134: 642–643.

    Article  PubMed  Google Scholar 

  33. Spahn, Thomas W., Hermann Herbst, Paul D. Rennert, Norbert Lugering, Christian Maaser, Mathias Kraft, Adriano Fontana, Howard L. Weiner, Wolfram Domschke, and T. Kucharzik. 2002. Induction of colitis in mice deficient of Peyer’s patches and mesenteric lymph node is associated with increased disease severity and formation of colonic lymphoid patches. The American Journal of Pathology 161: 2273–2282.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank He Lihua, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, for cultivating H. pylori SS1.

Funding

This study was funded by the National Natural Science Foundation of China (grant number 81370515 and 81770549) and Beijing Natural Science Foundation (grant number 7162194).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jingtong Wang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Tan, J., Zhang, F. et al. H.pylori Infection Alleviates Acute and Chronic Colitis with the Expansion of Regulatory B Cells in Mice. Inflammation 42, 1611–1621 (2019). https://doi.org/10.1007/s10753-019-01022-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-019-01022-0

Key Words

Navigation