Drosophila Myc restores immune homeostasis of Imd pathway via activating miR-277 to inhibit imd/Tab2
Drosophila Myc restores immune homeostasis of Imd pathway via activating miR-277 to inhibit imd/Tab2
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DOI：
10.1371/journal.pgen.1008989
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发表时间：
2020-08-01
期刊：
影响因子：
4.5
通讯作者：
Ma, Fei
中科院分区：
文献类型：
--
作者：
Li, Ruimin;Zhou, Hongjian;Ma, Fei
先天免疫是抵抗病原微生物的第一道防线。免疫反应的过度激活和抑制都对生物体有害。调节免疫反应的持续时间和强度是必不可少的。本研究发现，果蝇Myc（dMyc）作为一种转录因子，在果蝇免疫中后期通过抑制fmd/Tab 2基因的表达，激活miR-277的转录，从而负调控Imd通路。dMyc是恢复果蝇免疫稳态以使果蝇在感染后存活所必需的。由于dMyc基因在动物体内高度保守，我们的研究结果对于理解动物先天免疫应答的复杂调控机制具有重要意义。果蝇Myc（dMyc）作为一种广谱转录因子，可以调控大量基因的表达，从而控制细胞周期进程、细胞生长、增殖和凋亡等多种细胞过程。然而，dMyc是否参与果蝇的免疫应答仍是未知数。在这里，我们通过功能丧失和获得筛选确定dMyc是果蝇Imd途径的负调节因子。我们证明dMyc通过直接激活miR-277的转录，进一步抑制mdd和Tab 2-Ra/B的表达，从而抑制果蝇的免疫应答。重要的是，dMyc可以提高感染后果蝇的存活率，表明dMyc阻断果蝇Imd通路对于恢复生存所必需的免疫稳态至关重要。综上所述，我们的研究不仅报道了一个新的dMyc-miR-277-imd/Tab 2轴参与果蝇Imd通路的负调控，而且为果蝇免疫稳态维持的复杂调控机制提供了新的见解。
Author summary Innate immunity is the first line of defense against pathogenic microorganisms. Both overactivation and depression of immune response are detrimental to the organism. It is indispensable to regulate the duration and intensity of immune response. In this work, we find thatDrosophilaMyc (dMyc) as a transcription factor activates the transcription of miR-277 to negatively regulate the Imd pathway via inhibiting the expression ofimd/Tab2gene in the middle and later stage ofDrosophilainnate immune. dMyc is required to restoreDrosophilaimmune homeostasis for the survival of flies upon infection. Since dMyc is well conserved in animals, our findings will be important in understanding the complex regulatory mechanisms of innate immune responses in animals.DrosophilaMyc (dMyc), as a broad-spectrum transcription factor, can regulate the expression of a large number of genes to control diverse cellular processes, such as cell cycle progression, cell growth, proliferation and apoptosis. However, it remains largely unknown about whether dMyc can be involved inDrosophilainnate immune response. Here, we have identified dMyc to be a negative regulator ofDrosophilaImd pathway via the loss- and gain-of-function screening. We demonstrate that dMyc inhibitsDrosophilaImd immune response via directly activatingmiR-277transcription, which further inhibit the expression ofimdandTab2-Ra/b. Importantly, dMyc can improve the survival of flies upon infection, suggesting inhibitingDrosophilaImd pathway by dMyc is vital to restore immune homeostasis that is essential for survival. Taken together, our study not only reports a new dMyc-miR-277-imd/Tab2 axis involved in the negative regulation ofDrosophilaImd pathway, and provides a new insight into the complex regulatory mechanism ofDrosophilainnate immune homeostasis maintenance.