Chen Chen, Yang Liangli, Abbas Muhammad Nadeem, Zou Deng, Li Jun, Geng Xuexia, Zhang Haijun, Sun Yuxuan
College of Life Sciences, Huaibei Normal University, Huaibei, 235000, China.
College of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.
Dev Comp Immunol. 2022 Jul;132:104406. doi: 10.1016/j.dci.2022.104406. Epub 2022 Mar 29.
In innate immunity, autophagy is an important molecular mechanism that plays a critical role in the animal defense system. Given the importance of anti-microbial autophagy in the innate immune processes, the relationship between anti-microbial autophagy and LPS-induced innate immunity in A. pernyi was investigated. Quantitative RT-PCR analysis revealed that autophagy-related genes (ATG6, ATG5, and ATG12) were induced following LPS injection. LPS treatment in the Relish knockdown larvae reduced the expression of autophagy-related genes, especially ATG5. Furthermore, ATG5 depletion decreased the innate immune effect, while its over-expression with ATG12 was induced after the LPS challenge. The dual-luciferase assay revealed that Relish could regulate ATG5 expression by binding directly to the promoter of the ATG5 gene. Overall, our findings show that Relish regulates the ATG5 transcription to eliminate Gram-negative bacteria by anti-microbial autophagy, implying a strong connection between autophagy and innate immunity in immunologic homeostasis.
在天然免疫中，自噬是一种重要的分子机制，在动物防御系统中发挥关键作用。鉴于抗微生物自噬在天然免疫过程中的重要性，本研究调查了柞蚕中抗微生物自噬与脂多糖（LPS）诱导的天然免疫之间的关系。定量逆转录聚合酶链反应（RT-PCR）分析显示，注射LPS后自噬相关基因（ATG6、ATG5和ATG12）被诱导表达。在Relish基因敲低的幼虫中进行LPS处理，降低了自噬相关基因的表达，尤其是ATG5。此外，ATG5基因缺失降低了天然免疫效应，而在LPS刺激后，其与ATG12共同过表达。双荧光素酶报告基因检测显示，Relish可通过直接结合ATG5基因的启动子来调节ATG5的表达。总体而言，我们的研究结果表明，Relish通过调节ATG5转录，通过抗微生物自噬消除革兰氏阴性菌，这意味着自噬与天然免疫在免疫稳态中存在紧密联系。
