Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.
Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.
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阳离子氨基酸转运蛋白2增强了幽门螺杆菌感染期间的先天免疫力。
DOI：
10.1371/journal.pone.0029046
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wilson KT
中科院分区：
文献类型：
--
作者：
Barry DP;Asim M;Scull BP;Piazuelo MB;de Sablet T;Lewis ND;Coburn LA;Singh K;Ellies LG;Gobert AP;Chaturvedi R;Wilson KT
一旦获得，幽门螺杆菌感染是终身的，由于先天性和适应性免疫应答不足。我们以前的研究表明，宿主精氨酸代谢的各种途径之间的相互作用是感染后结果的关键决定因素。阳离子氨基酸转运蛋白2（CAT 2）是H.幽门感染一旦在细胞内，这种氨基酸被相反的途径利用，导致从诱导型NO合酶（iNOS）产生的杀菌性一氧化氮（NO）或过氧化氢的产生，过氧化氢通过过氧化物酶和多胺途径引起巨噬细胞凋亡。由于CAT 2在控制巨噬细胞中L-Arg利用率方面发挥着核心作用，我们研究了CAT 2在H期间体内的重要性。幽门感染与野生型小鼠相比，感染4个月的CAT 2 −/−小鼠表现出胃炎减少和定植水平增加。我们观察到胃巨噬细胞水平的抑制，巨噬细胞iNOS的表达，树突状细胞活化，以及CAT 2 −/−小鼠中粒细胞集落刺激因子的表达，表明CAT 2参与增强先天免疫反应。此外，CAT 2 −/−小鼠中的细胞因子表达从抗微生物Th 1应答改变为Th 2应答，表明转运蛋白对获得性免疫也有下游效应。这些发现表明CAT 2是H.幽门感染
Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2) is essential for transport of l-arginine (L-Arg) into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO) produced from inducible NO synthase (iNOS), or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2−/− mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2−/− mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2−/− mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.
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影响因子：
29.4
作者：
Lee, A;ORourke, J;Dixon, MF
通讯作者：
Dixon, MF
影响因子：
3.1
作者：
Kranzer, K;Eckhardt, A;Schneider-Brachert, W
通讯作者：
Schneider-Brachert, W
影响因子：
--
作者：
Andres, Sonke;Schmidt, Heather-Marie A.;Engstrand, Lars
通讯作者：
Engstrand, Lars
影响因子：
4.8
作者：
Chaturvedi, R;Cheng, YL;Wilson, KT
通讯作者：
Wilson, KT
影响因子：
4.4
作者：
Gobert, AP;Mersey, BD;Wilson, KT
通讯作者：
Wilson, KT