Wang Jinli, Wu Minhao, Wen Jinsheng, Yang Kun, Li Miao, Zhan Xiaoxia, Feng Lianqiang, Li Meiyu, Huang Xi
Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, China.
Mol Immunol. 2014 Nov;62(1):29-36. doi: 10.1016/j.molimm.2014.05.012. Epub 2014 Jun 14.
Macrophages play a critical role in the host immune response against mycobacterial infection. Our previous study has demonstrated that microRNA-155 (miR-155), one of the most important small non-coding RNAs in the immune system, promotes oxygen-independent mycobacterial killing in macrophages. However, little is known regarding the role of miR-155 in modulating oxygen-dependent mycobactericidal response in macrophages, including the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In the present study, we demonstrated that miR-155 was increased in macrophages after Mycobacterium bovis bacille Calmette-Guérin (BCG) infection. Moreover, the BCG-induced upregulation of miR-155 in macrophages was dependent on TLR2, NF-κB and JNK signaling pathways. More importantly, our study explored that miR-155 significantly elevated ROS production in macrophages, although miR-155 had no influence on the inducible nitric oxide synthase (iNOS) expression or nitric oxide (NO) production. In addition, our study demonstrated that miR-155 repressed the expression of src homology 2 (SH2) containing inositol 5-phosphatase1 (SHIP1), and knockdown of SHIP1 greatly increased ROS production in BCG-infected macrophages. Collectively, these data indicate that miR-155 modulates ROS but not RNS production by targeting SHIP1, which may provide a better understanding of the host anti-mycobacterial response.
巨噬细胞在宿主针对分枝杆菌感染的免疫反应中发挥关键作用。我们之前的研究表明，微小RNA-155（miR-155）是免疫系统中最重要的小非编码RNA之一，可促进巨噬细胞中不依赖氧气的分枝杆菌杀伤作用。然而，关于miR-155在调节巨噬细胞中依赖氧气的杀菌反应中的作用，包括活性氧（ROS）和活性氮（RNS）的产生，我们知之甚少。在本研究中，我们证明牛分枝杆菌卡介苗（BCG）感染后巨噬细胞中miR-155水平升高。此外，BCG诱导的巨噬细胞中miR-155上调依赖于TLR2、NF-κB和JNK信号通路。更重要的是，我们的研究发现，尽管miR-155对诱导型一氧化氮合酶（iNOS）表达或一氧化氮（NO）产生没有影响，但它能显著提高巨噬细胞中ROS的产生。此外，我们的研究表明，miR-155可抑制含src同源2（SH2）结构域的肌醇5-磷酸酶1（SHIP1）的表达，敲低SHIP1可显著增加BCG感染巨噬细胞中ROS的产生。总的来说，这些数据表明miR-155通过靶向SHIP1调节ROS而非RNS的产生，这可能有助于更好地理解宿主抗分枝杆菌反应。
