Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila
Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila
复制标题
多元醇途径的糖醇作为警报素介导果蝇局部系统先天免疫通讯
DOI：
10.1016/j.chom.2019.07.001
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发表时间：
2019-08-14
影响因子：
30.3
通讯作者：
Pan, Lei
中科院分区：
文献类型：
--
作者：
Yang, Shuo;Zhao, Yaya;Pan, Lei
器官间免疫通讯是连接局部系统先天免疫反应和协调稳态宿主防御的关键。然而，这些因素及其在这一过程中的作用仍不清楚。我们发现果蝇肠道内的IMD反应可以依次触发脂肪体的系统性IMD反应。多元醇途径中的糖醇对肠-脂体免疫通讯（GFIC）的时空调节至关重要。肠道内IMD的激活导致血淋巴中山梨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，是血浆糖醇升高的必要和充分条件。山梨醇通过随后的金属蛋白酶2的激活来介导GFIC，金属蛋白酶2裂解PGRP-LC来激活脂肪体的IMD反应。因此，这项工作揭示了GFIC如何依赖于血淋巴多元醇途径的中间激活，并证明AR在全局炎症反应中提供了一个关键的代谢检查点。
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.