Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.
Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.
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DOI：
10.1371/journal.pone.0078191
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
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
大约10-15%感染幽门螺杆菌的个体会发展为溃疡病（胃溃疡或十二指肠溃疡），而大多数感染幽门螺杆菌的人会发展为胃溃疡或十二指肠溃疡。pylori将无症状。大多数感染者保持无症状，部分原因是H. pylori细胞壁的α 1，4-GlcNAc-帽粘蛋白O-聚糖，其在胃粘膜的较深部分中表达。然而，尚未确定形成胆固醇α-葡萄糖苷的胆固醇α-葡萄糖基转移酶（αCgT）在H.幽门感染在此，我们证明了H.幽门螺杆菌临床分离株与胃萎缩程度高度相关。我们研究了胆固醇α-葡萄糖苷在免疫应答各个方面的作用。在野生型H. pylori或携带αCgT突变形式的变体，表现出一系列酶活性。然而，胆固醇α-葡萄糖苷被不变的自然杀伤T（iNKT）细胞识别，在体外和体内引发免疫应答。接种H. pylori携带高活性的αCgT进入iNKT细胞缺陷（Jα18−/−）或野生型小鼠，与野生型小鼠相比，Jα18−/−中的细菌回收率显著增加。此外，与野生型小鼠相比，Jα18−/−中Th 1和Th 2细胞的细胞因子产生特征显著降低。这些发现表明胆固醇α-葡萄糖苷在H.幽门介导的胃炎和癌前萎缩性胃炎。
Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides 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 αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.
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DOI：
10.1084/jem.191.1.115
发表时间：
2000-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen LA;Schlesinger LS;Kang B
通讯作者：
Kang B
影响因子：
24.5
作者：
Hidaka, E;Ota, H;Katsuyama, T
通讯作者：
Katsuyama, T
影响因子：
15.9
作者：
Chang, Ya-Jen;Kim, Hye Young;Umetsu, Dale T.
通讯作者：
Umetsu, Dale T.
影响因子：
3.2
作者：
HIRAI, Y;HAQUE, M;OGUMA, K
通讯作者：
OGUMA, K
影响因子：
30.5
作者：
Kinjo, Yuki;Tupin, Emmanuel;Kronenberg, Mitchell
通讯作者：
Kronenberg, Mitchell