Aims
Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria.
Background & aims
Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria.
Conclusions
Gastric stromal factors down-regulate DC responsiveness to H pylori, resulting in a dampened gastric Th1 response. We speculate that stroma-induced down-regulation of DC function contributes to the permissiveness of both gastric and intestinal mucosa to colonization by persistent residential microbes.
Methods
To model mucosal DC development, we isolated and cultured cell-depleted human stroma/extracellular matrix from fresh gastric and intestinal mucosa to generate stroma-conditioned media. We then analyzed the capacity of stroma-conditioned media-treated monocyte-derived DCs and primary human gastric and intestinal DCs pulsed in vitro with H pylori to induce T-cell proliferation and interferon gamma secretion.
Results
Stromal factors in gastric mucosa suppressed H pylori-stimulated DC activation and the ability of DCs to drive a Th1 proliferative and cytokine response to H pylori. The ability of gastric stromal factors to down-regulate DC function was similar to that of intestinal stromal factors and was independent of transforming growth factor β, prostaglandin E&sub2;, interleukin (IL)-10, and thymic stromal lymphopoietin. Stroma-conditioned media-induced reduction in DC-stimulated Th1 responses was associated with reduced DC release of IL-12. Conclusions: Gastric stromal factors down-regulate DC responsiveness to H pylori, resulting in a dampened gastric Th1 response. We speculate that stroma-induced down-regulation of DC function contributes to the permissiveness of both gastric and intestinal mucosa to colonization by persistent residential microbes.