Helicobacter pylori immune escape is mediated by dendritic cell–induced Treg skewing and Th17 suppression in mice

JY Kao, M Zhang, MJ Miller, JC Mills, B Wang, M Liu… - Gastroenterology, 2010 - Elsevier
JY Kao, M Zhang, MJ Miller, JC Mills, B Wang, M Liu, KA Eaton, W Zou, BE Berndt, TS Cole
Gastroenterology, 2010Elsevier
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 …
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.
Elsevier