Helicobacter pylori infected gastric epithelial cells drive dendritic cells towards a tolerogenic phenotype

Abstract The interactions of dendritic cells (DCs) with the gastric epithelium are thought to play a role in shaping DC function and thus the adaptive immune response to Helicobacter pylori (H. pylori) infection. We have shown that DCs are recruited to the H. pylori-infected gastric epithelium, positioning them for uptake of bacterial antigen from the gastric lumen. Using a gastric organoid model of H. pylori infection, we sought to define how the interactions between gastric epithelial cells and DCs regulate the antigen-presenting cell capacity of DCs. Supernatants were collected from organoids microinjected with H. pylori (infected) or PBS (mock), and monocyte-derived dendritic cells (MoDCs) were incubated with these supernatants. Flow cytometry data showed that the supernatant from infected organoids drove the DCs toward a tolerogenic state, as the expression of CD40, CD83, and CD86 was significantly decreased compared to incubation with supernatants from mock infected organoids, whereas CCR7 expression was increased consistent with a more tolerogenic phenotype. DCs treated with supernatants from infected, but not mock-infected organoids suppressed the proliferation of naïve autologous T cells. We also assessed T cell polarization using a cytokine array and found an increase in Th1, Th17 and Treg cytokines, but a decrease in Th2 cytokines in T cells that were challenged with DCs pre-treated with supernatants from infected organoids compared to mock-infected organoids. In summary, we have shown that H. pylori-infected gastric epithelium drives the DCs toward a tolerogenic state, resulting in reduced expression of maturation markers and CD4+ T cell proliferation while maintaining the DCs’ ability to induce T cell cytokine secretion.