Dual roles of CagA protein in Helicobacter pylori-induced chronic gastritis in mice
Dual roles of CagA protein in Helicobacter pylori-induced chronic gastritis in mice
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DOI：
10.1016/j.bbrc.2011.07.081
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发表时间：
2011-08-26
影响因子：
3.1
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
--
作者：
Kido, Masahiro;Watanabe, Norihiko;Chiba, Tsutomu
细胞毒素相关基因A（CagA）直接作用于胃上皮细胞。CagA在宿主抗幽门螺杆菌（Helicobacter pylori，H. pylori）感染尚未完全了解。本研究旨在探讨CagA在H. pylori诱导的慢性胃炎，我们使用了一种过继转移模型，其中来自C57 BL/6小鼠的脾细胞有或没有H. pylori感染转移到RAG 2（-/-）小鼠中，具有CagA（+）H的胃定植。pylori或CagA（-）H。幽门。CagA（+）H. pylori感染而非CagA（-）H感染。pylori感染的RAG 2（-/-）小鼠，其胃粘膜内的幽门螺杆菌感染可引起严重的慢性胃炎。未感染幽门的小鼠。此外，CagA（+）H.将pylori致敏的脾细胞转移到RAG 2（-/-）小鼠体内，仅在感染CagA（+）H的RAG 2（-/-）小鼠胃粘膜中观察到CD 4（+）T细胞浸润。pylori感染而非CagA（-）H感染。pylori感染，提示CagA（+）H. pylori在宿主胃粘膜中的迁移是必不可少的。幽门致敏的CD 4（+）T细胞。CagA（-）H. pylori致敏的脾细胞转化为CagA（+）H。pylori感染的RAG 2（-/-）小鼠与CagA（+）H转移相比，诱导更严重的慢性胃炎，Foxp 3（+）调节性T细胞浸润更少。幽门致敏的脾细胞。结论胃内CagA在H.幽门螺杆菌致敏的CD 4（+）T细胞在胃粘膜中表达，而CagA依赖的T细胞致敏诱导调节性T细胞分化，提示CagA在H.幽门螺杆菌引起的慢性胃炎(C)2011 Elsevier Inc. All rights reserved.
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. (C) 2011 Elsevier Inc. All rights reserved.