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Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis
  1. Jay Luther1,
  2. Stephanie Y Owyang1,
  3. Tomomi Takeuchi1,
  4. Tyler S Cole1,
  5. Min Zhang1,
  6. Maochang Liu1,
  7. John Erb-Downward1,
  8. Joel H Rubenstein1,2,
  9. Chun-Chia Chen3,
  10. Anna V Pierzchala1,
  11. Jose A Paul1,
  12. John Y Kao1
  1. 1Department of Internal Medicine (Division of Gastroenterology), University of Michigan Health System, Ann Arbor, Michigan, USA
  2. 2Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
  3. 3Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan
  1. Correspondence to Dr John Y Kao, Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, 6520A MSRB I, SPC 5682, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5682, USA; jykao{at}umich.edu

Abstract

Background and aims Epidemiological data have recently emerged to suggest Helicobacter pylori may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between H pylori and IBD has not been described.

Methods The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow-derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (DC) was analysed by cytokine production. The effect of H pylori DNA on Escherichia coli DNA production of type I IFN and IL-12 was assessed. The in-vivo significance of H pylori DNA suppression was assessed in a dextran sodium sulphate (DSS) model of colitis. The systemic levels of type I IFN were assessed in H pylori-colonised and non-colonised patients.

Results H pylori DNA has a significantly elevated IRS:ISS ratio. In-vitro experiments revealed the inability of H pylori DNA to stimulate type I IFN or IL-12 production from mouse BMDC or human plasmacytoid DC. H pylori DNA was also able to suppress E coli DNA production of type I IFN and IL-12. The administration of H pylori DNA before the induction of DSS colitis significantly ameliorated the severity of colitis compared with E coli DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in H pylori-colonised patients than non-colonised controls.

Conclusions This study indicates that H pylori DNA has the ability to downregulate pro-inflammatory responses from DC and this may partly explain the inverse association between H pylori and IBD.

  • Dendritic cells
  • Helicobacter pylori
  • IBD
  • inflammatory bowel disease
  • mucosal immunology

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Footnotes

  • JL and SYO both contributed equally to this paper.

  • Funding This study was supported by grants from the National Institutes of Health (1 F32 DK084694-01A1 to JL, 1 KO8 DK0669907-01 and 1 R03 DK081678-01 to JYK and K23DK079291 to JHR) and AGA–Broad Foundation Student Research Fellowship Award (SYO).

  • Competing intersets None.

  • Ethics approval This study was conducted with the approval of the University of Michigan Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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