Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in N -glycanase 1 deficient Drosophila.
Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in N -glycanase 1 deficient Drosophila.
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肠道屏障缺陷、肠道先天免疫反应增强以及脂质分解代谢增强导致 N-聚糖酶 1 缺陷的果蝇致死。
DOI：
10.1101/2023.04.07.536022
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Jafar-Nejad,Hamed
中科院分区：
文献类型：
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作者：
Pandey,Ashutosh;Galeone,Antonio;Han,SeungYeop;Story,BenjaminA;Consonni,Gaia;Mueller,WilliamF;Steinmetz,LarsM;Vaccari,Thomas;Jafar-Nejad,Hamed
肠屏障功能障碍会导致炎症和相关的代谢变化。然而，在屏障功能障碍的背景下，感染和非感染机制对动物健康的相对影响还没有被很好地理解。在这里，我们证实了果蝇N-糖聚糖酶1(Png1)的缺失会导致肠道屏障缺陷，从而导致饥饿和JNK活性增加。这些缺陷导致FOXO过度激活，从而诱导高度活跃的先天免疫反应和脂质分解代谢，从而导致与Png1丢失相关的致命性。值得注意的是，无菌饲养突变体并不能挽救致命性。相比之下，在等卡路里、富含脂肪的饮食中饲养Pnglu突变体可以以剂量依赖的方式提高动物的存活率。我们的数据表明，Png1在果蝇幼虫体内起着建立肠道屏障的作用，Pngl缺失的免疫和代谢后果主要是通过非感染性机制介导的。
Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss ofDrosophila N-glycanase 1 (Pngl) leads to gut barrier defects, which cause starvation and increased JNK activity. These defects result in Foxo overactivation, which induces a hyperactive innate immune response and lipid catabolism, thereby contributing to lethality associated with loss ofPngl. Notably, germ-free rearing ofPnglmutants did not rescue lethality. In contrast, raisingPnglmutants on isocaloric, fat-rich diets improved animal survival in a dosage-dependent manner. Our data indicate that Pngl functions inDrosophilalarvae to establish the gut barrier, and that the immune and metabolic consequences of loss ofPnglare primarily mediated through non-infectious mechanisms.