Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila.,Cell Host & Microbe

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Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2019-07-23 , DOI: 10.1016/j.chom.2019.07.001
Shuo Yang ₁ , Yaya Zhao ₂ , Junjing Yu ₃ , Zhiqin Fan ₄ , Si-Tang Gong ₅ , Hong Tang ₂ , Lei Pan ₁

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Interorgan immunological communication is critical to connect the local-systemic innate immune response and orchestrate a homeostatic host defense. However, the factors and their roles in this process remain unclear. We find Drosophila IMD response in guts can sequentially trigger a systemic IMD reaction in the fat body. Sugar alcohols of the polyol pathway are essential for the spatiotemporal regulation of gut-fat body immunological communication (GFIC). IMD activation in guts causes elevated levels of sorbitol and galactitol in hemolymph. Aldose reductase (AR) in hemocytes, the rate-limiting enzyme of the polyol pathway, is necessary and sufficient for the increase of plasma sugar alcohols. Sorbitol relays GFIC by subsequent activation of Metalloprotease 2, which cleaves PGRP-LC to activate IMD response in fat bodies. Thus, this work unveils how GFIC relies on the intermediate activation of the polyol pathway in hemolymph and demonstrates that AR provides a critical metabolic checkpoint in the global inflammatory response.

中文翻译：

多元醇途径的糖醇用作警报蛋白，以介导果蝇中的局部系统先天免疫通讯。

器官间的免疫学交流对于连接局部系统的先天免疫反应和协调体内的宿主防御至关重要。但是，在此过程中的因素及其作用仍不清楚。我们发现果蝇中的果蝇IMD反应可以依次触发脂肪体内的系统性IMD反应。多元醇途径的糖醇对于时空调节肠道脂肪身体的免疫学交流（GFIC）是必不可少的。内脏中的IMD激活会导致血淋巴中的山梨糖醇和半乳糖醇水平升高。血细胞中的醛糖还原酶（AR）是多元醇途径的限速酶，对于增加血浆糖醇而言是必要和充分的。山梨糖醇通过随后激活金属蛋白酶2来中继GFIC，该酶裂解PGRP-LC以激活脂肪体中的IMD反应。因此，

更新日期：2019-07-23

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