The Relish/miR-275/Dredd mediated negative feedback loop is crucial to restoring immune homeostasis of Drosophila Imd pathway

IF 3.2 2区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wanwan Pan , Xiaolong Yao , Lu Lin, Xiaoqi Liu, Ping Jin, Fei Ma
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Abstract

The NF-κB/Relish, as a core transcription factor of Drosophila immune deficiency (Imd) pathway, activates the transcriptions of antimicrobial peptides (AMPs) to combat gram-negative bacterial infections, but its role in regulating miRNA expression during immune response has less been reported. We here describe a negative feedback loop of Imd signaling mediated by Relish/miR-275/Dredd that controls Drosophila immune homeostasis after Escherichia coli (E. coli) infection. Our results demonstrate that Relish may directly activate the transcription of miR-275 via binding to its promoter in vitro and vivo, particularly miR-275 further inhibits the expression of Dredd through binding to its 3′UTR to negatively control Drosophila Imd immune response. Remarkably, the ectopic expression of miR-275 significantly reduces Drosophila lifespan. More importantly, our work uncovers a new mechanism by which Relish can flexibly switch its role to maintain Drosophila immune response and homeostasis during infection. Collectively, our study not only reveals the functional duality of Relish in regulating immune response of Drosophila Imd pathway, but also provides a new insight into the maintenance of animal innate immune homeostasis.

Abstract Image

Relish/miR-275/Dredd介导的负反馈回路对恢复果蝇Imd通路的免疫稳态至关重要。
NF-κB/Relish作为果蝇免疫缺陷(Imd)途径的核心转录因子,激活抗菌肽(AMPs)的转录以对抗革兰氏阴性细菌感染,但其在免疫反应过程中调节miRNA表达的作用较少报道。我们在这里描述了由Relish/miR-275/Dredd介导的Imd信号传导的负反馈回路,该回路在大肠杆菌(E.coli)感染后控制果蝇的免疫稳态。我们的研究结果表明,Relish可以通过在体外和体内结合其启动子直接激活miR-275的转录,特别是miR-275通过结合其3’UTR进一步抑制Dredd的表达,从而负面控制果蝇Imd的免疫反应。值得注意的是,miR-275的异位表达显著缩短了果蝇的寿命。更重要的是,我们的工作揭示了一种新的机制,通过这种机制,Relish可以灵活地转换其角色,以在感染期间维持果蝇的免疫反应和稳态。总之,我们的研究不仅揭示了Relish在调节果蝇免疫应答途径中的功能双重性,而且为维持动物先天免疫稳态提供了新的见解。
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来源期刊
CiteScore
7.40
自引率
5.30%
发文量
105
审稿时长
40 days
期刊介绍: This international journal publishes original contributions and mini-reviews in the fields of insect biochemistry and insect molecular biology. Main areas of interest are neurochemistry, hormone and pheromone biochemistry, enzymes and metabolism, hormone action and gene regulation, gene characterization and structure, pharmacology, immunology and cell and tissue culture. Papers on the biochemistry and molecular biology of other groups of arthropods are published if of general interest to the readership. Technique papers will be considered for publication if they significantly advance the field of insect biochemistry and molecular biology in the opinion of the Editors and Editorial Board.
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