MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection.
MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection.
复制标题
MicroRNA-106a通过靶向ULK1、ATG7和ATG16L1抑制分枝杆菌感染过程中的自噬过程和抗菌反应
DOI：
10.3389/fimmu.2020.610021
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Guo L
中科院分区：
文献类型：
--
作者：
Liu K;Hong D;Zhang F;Li X;He M;Han X;Zhang G;Xu G;Stonehouse NJ;Jiang Z;An W;Guo L
自噬是针对包括结核分枝杆菌（M. tuberculosis）在内的入侵病原体的先天免疫反应的关键要素。 microRNA 在调节宿主针对结核分枝杆菌的抗菌反应中的新兴作用已引起广泛关注。然而，miRNA 在分枝杆菌感染期间特异性影响抗菌自噬的过程在很大程度上尚不清楚。在这项研究中，我们证明了 miR-106a 在调节巨噬细胞自噬对抗结核分枝杆菌方面的新作用。 H37Ra 感染导致 miR-106a 以时间和剂量依赖性方式下调，并同时上调 THP-1 巨噬细胞中的三个靶标（ULK1、ATG7 和 ATG16L1）。 MiR-106a 可以通过靶向 ULK1、ATG7 和 ATG16L1 来抑制自噬激活和对结核分枝杆菌的抗菌反应。 miR-106a 的过表达显着抑制 H37Ra 诱导的人 THP-1 巨噬细胞自噬激活，而 miR-106a 的抑制剂显着促进 H37Ra 诱导的自噬。透射电子显微镜（TEM）观察也证实了miR-106a对分枝杆菌感染过程中自噬过程的抑制作用。更重要的是，miR-106a的强制表达增加了分枝杆菌的存活率，而用miR-106a抑制剂转染则减弱了细胞内分枝杆菌的存活率。综上所述，这些数据表明，在结核分枝杆菌感染过程中，miR-106a 通过靶向 ULK1、ATG7 和 ATG16L1，在自噬和抗菌作用中发挥负调节作用，这可能为开发结核病诊断试剂或抗菌药物提供潜在靶点。
Autophagy is a key element of innate immune response against invading pathogens including Mycobacterium tuberculosis (M. tuberculosis). The emerging roles of microRNAs in regulating host antimicrobial responses against M. tuberculosis have gained widespread attention. However, the process by which miRNAs specifically influence antibacterial autophagy during mycobacterial infection is largely uncharacterized. In this study, we demonstrate a novel role of miR-106a in regulating macrophage autophagy against M. tuberculosis. H37Ra infection leads to downregulation of miR-106a in a time- and dose-dependent manner and concomitant upregulation of its three targets (ULK1, ATG7, and ATG16L1) in THP-1 macrophages. MiR-106a could inhibit autophagy activation and antimicrobial responses to M. tuberculosis by targeting ULK1, ATG7, and ATG16L1. Overexpression of miR-106a dramatically inhibited H37Ra-induced activation of autophagy in human THP-1 macrophages, whereas inhibitors of miR-106a remarkably promoted H37Ra-induced autophagy. The inhibitory effect of miR-106a on autophagy process during mycobacterial infection was also confirmed by Transmission Electron Microscope (TEM) observation. More importantly, forced expression of miR-106a increased mycobacterial survival, while transfection with miR-106a inhibitors attenuated the survival of intracellular mycobacteria. Taken together, these data demonstrated that miR-106a functioned as a negative regulator in autophagy and antimicrobial effects by targeting ULK1, ATG7, and ATG16L1 during M. tuberculosis infection, which may provide a potential target for developing diagnostic reagents or antibacterials against tuberculosis.
登录
查看更多内容
影响因子：
5.6
作者：
Gruszka R;Zakrzewska M
通讯作者：
Zakrzewska M
影响因子：
8.5
作者：
Long J;He Q;Yin Y;Lei X;Li Z;Zhu W
通讯作者：
Zhu W
MicroRNA-27a 通过调节钙相关自噬来控制结核分枝杆菌的细胞内存活
影响因子：
16.6
作者：
Liu F;Chen J;Wang P;Li H;Zhou Y;Liu H;Liu Z;Zheng R;Wang L;Yang H;Cui Z;Wang F;Huang X;Wang J;Sha W;Xiao H;Ge B
通讯作者：
Ge B
影响因子：
30.5
作者：
Ouimet M;Koster S;Sakowski E;Ramkhelawon B;van Solingen C;Oldebeken S;Karunakaran D;Portal-Celhay C;Sheedy FJ;Ray TD;Cecchini K;Zamore PD;Rayner KJ;Marcel YL;Philips JA;Moore KJ
通讯作者：
Moore KJ
影响因子：
--
作者：
Jin J;Britschgi A;Schläfli AM;Humbert M;Shan-Krauer D;Batliner J;Federzoni EA;Ernst M;Torbett BE;Yousefi S;Simon HU;Tschan MP
通讯作者：
Tschan MP