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

作者：Kido Masahiro; Watanabe Norihiko; Aoki Nobuhiro; Iwamoto Satoru; Nishiura Hisayo; Maruoka Ryutaro; Ikeda Aki; Azuma Takeshi; Chiba Tsutomu^*

来源：Biochemical and Biophysical Research Communications, 2011, 412(2): 266-272.

DOI：10.1016/j.bbrc.2011.07.081

• Cytotoxin-associated gene A
• Helicobacter pylori
• Chronic gastritis

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.

• 出版日期2011-8-26