Yao Xiaolong, He Yuqing, Zhu Canhe, Yang Shangmin, Wu Jing, Ma Fei, Jin Ping
Laboratory for Molecular Immunity and Bioinformatics & Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China.
Department of Psychology, College of Victoria College, University of Toronto, Toronto, ON, M5R 0A3, Canada.
Microbes Infect. 2024 Nov-Dec;26(8):105399. doi: 10.1016/j.micinf.2024.105399. Epub 2024 Jul 29.
The Drosophila Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after Escherichia coli infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases Drosophila survival rates upon lethal Enterobacter cloacae infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of Tab2. In addition, the dynamic expression pattern of AMPs (Dpt, AttA, CecA1), miR-190 and Tab2 in the wild-type flies reveals that miR-190 play an important role in Drosophila immune homeostasis restoration at the late stage of E. coli infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting Tab2 and promote immune homeostasis restoration in Drosophila Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.
果蝇的Imd通路是参与先天性免疫的著名机制，负责革兰氏阴性（G-）细菌感染。免疫的强度和持久性需要精确调节，以保持足够的免疫激活，同时避免过度的免疫反应。在本研究中，我们首先使用miR-190过表达果蝇和miR-190KO/+果蝇证明，在大肠杆菌感染后，miR-190可以下调Imd免疫通路中抗菌肽（AMPs）的表达水平。其次，miR-190过表达显著降低了果蝇在致死性阴沟肠杆菌感染后的存活率，而miR-190基因敲除则提高了存活率。第三，我们进一步证明，miR-190通过直接靶向Tab2的RA/RB和RC亚型来负向调节先天性免疫反应。此外，野生型果蝇中AMPs（Dpt、AttA、CecA1）、miR-190和Tab2的动态表达模式表明，miR-190在大肠杆菌感染后期的果蝇免疫稳态恢复中起重要作用。总之，我们的研究表明，miR-190可以通过靶向Tab2下调AMPs的表达，并促进果蝇Imd通路中免疫稳态的恢复。我们的研究为动物先天性免疫稳态的调节机制提供了新的见解。
