Institute for Translational Medicine, Qingdao University, Qingdao 266021, China.
Institute for Translational Medicine, Qingdao University, Qingdao 266021, China; Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang 261053, China.
Fish Shellfish Immunol. 2018 Apr;75:32-40. doi: 10.1016/j.fsi.2018.01.036. Epub 2018 Feb 1.
The innate immune system is the first line defense mechanism that recognizes, responds to, controls or eliminates invading pathogens. Toll-like receptors (TLRs) are a critical family of pattern recognition receptors (PRRs) tightly regulated by complex mechanisms involving many molecules to ensure a beneficial outcome in response to foreign invaders. MicroRNAs (miRNAs), a transcriptional and posttranscriptional regulator family in a wide range of biological processes, have been identified as new molecules related to the regulation of TLR-signaling pathways in immune responses. To date, at least 22 TLR types have been identified in more than a dozen different fish species. However, the functions and underlying mechanisms of miRNAs in the regulation of inflammatory responses related to the TLR-signaling pathway in fish is lacking. In this review, we summarize the regulation of miRNA expression profiles in the presence of TLR ligands or pathogen infections in teleost fish. We focus on the effects of miRNAs in regulating TLR-signaling pathways by targeting multiple molecules, including TLRs themselves, TLR-associated signaling proteins, and TLR-induced cytokines. An understanding of the relationship between the TLR-signaling pathways and miRNAs may provide new insights for drug intervention to manipulate immune responses in fish.
固有免疫系统是识别、响应、控制或消除入侵病原体的第一道防线。Toll 样受体 (TLR) 是一类重要的模式识别受体 (PRR),其受到涉及多种分子的复杂机制的严格调控,以确保对外国入侵者产生有益的结果。MicroRNAs (miRNAs) 是一个在广泛的生物学过程中具有转录和转录后调节功能的家族,已被确定为与免疫反应中 TLR 信号通路调节相关的新分子。迄今为止,在十几种不同的鱼类中已经鉴定出至少 22 种 TLR 类型。然而,miRNAs 在调节鱼类 TLR 信号通路相关炎症反应中的功能和潜在机制尚不清楚。在这篇综述中,我们总结了 TLR 配体或病原体感染存在时,硬骨鱼类中 miRNA 表达谱的调节。我们重点关注 miRNA 通过靶向多种分子(包括 TLR 本身、TLR 相关信号蛋白和 TLR 诱导的细胞因子)来调节 TLR 信号通路的作用。了解 TLR 信号通路和 miRNAs 之间的关系可能为药物干预提供新的见解,以操纵鱼类的免疫反应。