Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell-Induced Treg Skewing and Th17 Suppression in Mice

John Y. Kao, Min Zhang, Mark J. Miller, Jason C. Mills, Baomei Wang, Maochang Liu, Kathyn A. Eaton, Weiping Zou, Bradford E. Berndt, Tyler S. Cole, Tomomi Takeuchi, Stephanie Y. Owyang, Jay Luther

Research output: Contribution to journalArticlepeer-review

229 Scopus citations

Abstract

Background & Aims: Helicobacter pylori infection increases gastric regulatory T cell (Treg) response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells (DCs) and thus inhibits interleukin-17+ helper T cells (Th17) immunity. Methods: Two-photon microscopy was used to locate DCs in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow-derived DCs was analyzed by cytokine production and stimulation of T-cell proliferation. The effect of VacA, CagA, transforming growth factor-β (TGF-β), and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori-specific Th17 response and H pylori density was determined by using anti-CD25 neutralizing antibodies to deplete Tregs in mice. Results: We showed that mucosal CD11c+ DCs are located near the surface of normal gastric epithelium, and their number increased after H pylori infection. Study of the direct interaction of DCs with H pylori showed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-β and IL-10. In vivo Treg skewing by adoptive transfer of H pylori-pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25+ Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori-specific Th17, but not Th1, response. Conclusions: Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance toward a Treg-biased response, which suppresses the effective induction of H pylori-specific Th17 immunity.

Original languageEnglish
Pages (from-to)1046-1054
Number of pages9
JournalGastroenterology
Volume138
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Dendritic Cells
  • H pylori
  • IL-17
  • Tregs

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