Xu Tianjun, Wang Yanjin, Li Jinrui, Shu Chang, Han Jingjing, Chu Qing
Laboratory of Fish Biogenetics & Immune Evolution, College of Marine Science, Zhejiang Ocean University, Zhoushan, 316022, China.
Laboratory of Fish Biogenetics & Immune Evolution, College of Marine Science, Zhejiang Ocean University, Zhoushan, 316022, China.
Fish Shellfish Immunol. 2016 Sep;56:336-348. doi: 10.1016/j.fsi.2016.07.024. Epub 2016 Jul 16.
Being indispensable pattern recognition receptors in innate immune responses in host protection, Toll-like receptors (TLRs) play an important role in pathogen recognition. Fish TLRs exhibit high variety and distinct features, although little is known about their function on ligand recognition and signaling pathway in fish. This paper reports the evolutionary spectrum of the TLR1 subfamily (referred to as TLR1, TLR6, and TLR10) as determined using the comparative genomic approach. We hypothesized that the TLR1 subfamily underwent two rounds of gene duplication events; the first duplication occurred prior to the divergence of amphibians, and the second one occurred prior to the divergence of eutherians. To further study the function of fish TLR1, we identified miiuy croaker (Miichthys miiuy) TLR1 (mmiTLR1) and determined its potential ability to perceive Vibrio anguillarum and lipopolysaccharide stimulation. Data further suggested that mmiTLR1 is dependent on TIRAP and MyD88 for signal transmission. In addition, immunocytochemistry showed the speculative interaction between MyD88 and mmiTLR1 TIR domain. Overall, we systematically and comprehensively analyzed evolution of TLR1 subfamily and the function of mmiTLR1, which will provide the basis for future scientific research on fish TLRs.
作为宿主防御中固有免疫反应中不可或缺的模式识别受体,Toll样受体(TLR)在病原体识别中发挥着重要作用。鱼类TLR表现出高度的多样性和独特特征,尽管人们对其在鱼类中识别配体和信号通路的功能了解甚少。本文报道了使用比较基因组学方法确定的TLR1亚家族(称为TLR1、TLR6和TLR10)的进化谱。我们假设TLR1亚家族经历了两轮基因复制事件;第一次复制发生在两栖动物分化之前,第二次复制发生在真兽类分化之前。为了进一步研究鱼类TLR1的功能,我们鉴定了大黄鱼(Miichthys miiuy)的TLR1(mmiTLR1),并确定了其感知鳗弧菌和脂多糖刺激的潜在能力。数据进一步表明,mmiTLR1信号传导依赖于TIRAP和MyD88。此外,免疫细胞化学显示了MyD88与mmiTLR1 TIR结构域之间的推测性相互作用。总体而言,我们系统全面地分析了TLR1亚家族的进化以及mmiTLR1的功能,这将为未来鱼类TLR的科学研究提供基础。