Dual roles of CagA protein in Helicobacter pylori-induced chronic gastritis in mice

Abstract Cytotoxin-associated gene A (CagA) acts directly on gastric epithelial cells. However, the roles of CagA in host adaptive immunity against Helicobacter pylori ( H. pylori ) infection are not fully understood. In this study, to investigate the roles of CagA in the development of H. pylori -induced chronic gastritis, we used an adoptive-transfer model in which spleen cells from C57BL/6 mice with or without H. pylori infection were transferred into RAG2 −/− mice, with gastric colonization of either CagA + H. pylori or CagA − H. pylori . Colonization of CagA + H. pylori but not CagA − H. pylori in the host gastric mucosa induced severe chronic gastritis in RAG2 −/− mice transferred with spleen cells from H. pylori -uninfected mice. In addition, when CagA + H. pylori -primed spleen cells were transferred into RAG2 −/− mice, CD4 + T cell infiltration in the host gastric mucosa were observed only in RAG2 −/− mice infected with CagA + H. pylori but not CagA − H. pylori , suggesting that colonization of CagA + H. pylori in the host gastric mucosa is essential for the migration of H. pylori -primed CD4 + T cells. On the other hand, transfer of CagA − H. pylori -primed spleen cells into CagA + H. pylori -infected RAG2 −/− mice induced more severe chronic gastritis with less Foxp3 + regulatory T-cell infiltration as compared to transfer of CagA + H. pylori -primed spleen cells. In conclusion, CagA in the stomach plays an important role in the migration of H. pylori -primed CD4 + T cells in the gastric mucosa, whereas CagA-dependent T-cell priming induces regulatory T-cell differentiation, suggesting dual roles for CagA in the pathophysiology of H. pylori -induced chronic gastritis.