Helicobacter pylori promotes dendritic cells maturation and inflammation via outer membrane vesicles.

Dendritic cells (DCs) are pivotal in mediating gastric inflammatory responses to Helicobacter pylori (H. pylori), a pathogen that infects half of the global population and contributes to gastric disorders. However, the mechanisms underlying the interaction between DCs and H. pylori remain poorly understood. This study shows that the proportion of mature DCs is significantly increased in gastric mucosal tissues of H. pylori-infected patients. Furthermore, we demonstrate that H. pylori promotes DCs maturation via the secretion of outer membrane vesicles (OMVs). H. pylori OMVs-mediated DCs maturation facilitates the differentiation of T lymphocytes into Th1 and Th17, resulting in the production of pro-inflammatory cytokines. Mechanistically, H. pylori OMVs enhance the binding of phosphorylated STAT3 to COX-2. We further identify that the bacterial effector CagA is partly responsible for OMVs-induced DCs maturation through the STAT3-COX-2-PGE2 pathway. Additionally, H. pylori OMVs augment lactic acid secretion from DCs, which promotes T lymphocytes proliferation and subsequent inflammatory responses. In summary, via OMVs secretion, H. pylori drives DCs maturation, thereby accelerating T lymphocytes activation and promoting pathogenic inflammation. These findings provide important insights for early intervention strategies aimed at eradicating H. pylori infection.