Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution.
Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution.
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DOI：
10.1038/ncomms11322
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发表时间：
2016-04-18
影响因子：
16.6
通讯作者：
Kim YJ
中科院分区：
文献类型：
--
作者：
Lee WB;Kang JS;Choi WY;Zhang Q;Kim CH;Choi UY;Kim-Ha J;Kim YJ
作为对持续性分枝杆菌感染的反应，宿主诱导肉芽肿，这通常不能根除细菌并导致组织损伤。不同的宿主受体需要控制肉芽肿的形成和解决，但很少有人知道他们的监管相互作用。在这里，我们表明，明克尔，分枝杆菌索因子的诱导受体，是巨噬细胞从细胞因子表达到高一氧化氮生产的关键开关。除了其对TLR介导的转录的刺激作用外，Mincle还通过p38和eIF5A hypusination增强了一氧化氮合成所需的关键基因的翻译，从而导致肉芽肿消退。因此，Mincle在使用转录和翻译控制的抗分枝杆菌防御过程中具有促进和随后解决炎症的双重功能。 分枝杆菌感染中肉芽肿的消退需要巨噬细胞从细胞因子转换为一氧化氮（NO）的产生。在这里，作者表明Mincle通过依赖于p38介导的eIF5A的hypusination的机制刺激关键NO合成基因的翻译。
In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution. Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls. Resolution of granulomas in mycobacterial infection requires macrophages to switch from cytokine to nitric oxide (NO) production. Here the authors show that Mincle stimulates translation of the key NO synthesis genes by a mechanism dependent on p38-mediated hypusination of eiF5A.