Helicobacter pylori cholesteryl alpha-glucosides contribute to immune response by natural killer T cells

幽门螺杆菌胆固醇 α-葡萄糖苷有助于自然杀伤 T 细胞的免疫反应

• 批准号: 24790388
• 负责人: ITO Yuki
• 金额: $ 2.83万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790388/
• 关键词: ヘリコバクター・ピロリ; 臨床分離株; 糖脂質; インバリアントNKT細胞

It has not been determined how cholesteryl alpha-glucosyltransferase (aCgT), which forms cholesteryl alpha-glucosides (aCGs), functions in the pathogenesis of H. pylori infection. We show that the activity of aCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of aCGs in various aspects of the immune response. aCGs were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active aCgT into iNKT cell-deficient (Ja18 KO) or wild-type mice, bacterial recovery significantly increased in Ja18 KO compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Ja18 KO compared to wild-type mice. These findings demonstrate that aCGs play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

尚未确定形成胆固醇α-葡糖苷（aCG）的胆固醇α-葡糖基转移酶（aCgT）如何在H.幽门感染结果表明，H.幽门螺杆菌临床分离株与胃萎缩程度高度相关。我们研究了aCG在免疫应答的各个方面的作用。aCG被不变的自然杀伤T（iNKT）细胞识别，在体外和体内引发免疫应答。接种H.将携带高活性aCgT的pylori感染到iNKT细胞缺陷型（Ja 18 KO）或野生型小鼠中，与野生型小鼠相比，Ja 18 KO中的细菌回收显著增加。此外，与野生型小鼠相比，Ja 18 KO中Th 1和Th 2细胞的细胞因子产生特征显著降低。这些发现表明aCGs在H.幽门介导的胃炎和癌前萎缩性胃炎。

项目成果

Pathological and immunological functions of cholesterylα-glucosides in Helicobacter pylori-associated inflammation

胆固醇α-葡萄糖苷在幽门螺杆菌相关炎症中的病理和免疫功能

• 发表时间: 2012
• 作者: Ito Y;Vela JL;Matsumura F;Hoshino H;Tyzniz A;Lee H;Girardi E;Zajonc MD;Kobayash M;Bao X;Boren T;Ito Y
• 通讯作者: Ito Y

Pathological and immunological functions of cholesteryl -glucosides in Helicobacter pylori-associated inflammation

胆固醇的病理和免疫功能

• 作者: Ito Y;Vela JL;Matsumura F;Hoshino H;Tyzniz A;Lee H;Girardi E;Zajonc MD;Kobayash M;Bao X;Boren T;Ito Y;Yuki Ito
• 通讯作者: Yuki Ito

ピロリ菌の持つコレステリル-α-グルコシド類の免疫学的機能

幽门螺杆菌胆固醇-α-葡萄糖苷的免疫功能

• 发表时间: 2013
• 作者: Ito Y;Vela JL;Matsumura F;Hoshino H;Tyznik A;Lee H;Girardi E;Zajonc DM;Liddington R;Kobayashi M;Bao X;Bugaytsova J;Boren T;Jin R;Zong Y;Seeberger PH;Nakayama J;Kronenberg M;Fukuda M;伊藤有紀
• 通讯作者: 伊藤有紀

Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.

• DOI: 10.1371/journal.pone.0078191
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ito Y;Vela JL;Matsumura F;Hoshino H;Tyznik A;Lee H;Girardi E;Zajonc DM;Liddington R;Kobayashi M;Bao X;Bugaytsova J;Borén T;Jin R;Zong Y;Seeberger PH;Nakayama J;Kronenberg M;Fukuda M
• 通讯作者: Fukuda M

Seeberger PH, Nakayama J, Kronenberg M, and Fukuda M. Helicobacter pylori cholesterylα-glucosides are critical for bacterial growth and activation of invariant NKT cells

Seeberger PH、Nakayama J、Kronenberg M 和 Fukuda M。幽门螺杆菌胆固醇α-葡萄糖苷对于细菌生长和恒定 NKT 细胞的激活至关重要

• 发表时间: 2012
• 作者: Ito Y;Vela JL;Matsumura F;Hoshino H;Tyzniz A;Lee H;Girardi E;Zajonc MD;Kobayash M;Bao X;Boren T
• 通讯作者: Boren T