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中国树鼩(Tupaia belangeri chinensis)中Toll样受体(TLRs)的鉴定与特性分析

Identification and characterization of toll-like receptors (TLRs) in the Chinese tree shrew (Tupaia belangeri chinensis).

作者信息

Yu Dandan, Wu Yong, Xu Ling, Fan Yu, Peng Li, Xu Min, Yao Yong-Gang

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.

出版信息

Dev Comp Immunol. 2016 Jul;60:127-38. doi: 10.1016/j.dci.2016.02.025. Epub 2016 Mar 8.

Abstract

In mammals, the toll-like receptors (TLRs) play a major role in initiating innate immune responses against pathogens. Comparison of the TLRs in different mammals may help in understanding the TLR-mediated responses and developing of animal models and efficient therapeutic measures for infectious diseases. The Chinese tree shrew (Tupaia belangeri chinensis), a small mammal with a close relationship to primates, is a viable experimental animal for studying viral and bacterial infections. In this study, we characterized the TLRs genes (tTLRs) in the Chinese tree shrew and identified 13 putative TLRs, which are orthologs of mammalian TLR1-TLR9 and TLR11-TLR13, and TLR10 was a pseudogene in tree shrew. Positive selection analyses using the Maximum likelihood (ML) method showed that tTLR8 and tTLR9 were under positive selection, which might be associated with the adaptation to the pathogen challenge. The mRNA expression levels of tTLRs presented an overall low and tissue-specific pattern, and were significantly upregulated upon Hepatitis C virus (HCV) infection. tTLR4 and tTLR9 underwent alternative splicing, which leads to different transcripts. Phylogenetic analysis and TLR structure prediction indicated that tTLRs were evolutionarily conserved, which might reflect an ancient mechanism and structure in the innate immune response system. Taken together, TLRs had both conserved and unique features in the Chinese tree shrew.

摘要

在哺乳动物中,Toll样受体(TLRs)在启动针对病原体的先天性免疫反应中起主要作用。比较不同哺乳动物中的TLRs可能有助于理解TLR介导的反应,并有助于开发针对传染病的动物模型和有效治疗措施。中国树鼩(Tupaia belangeri chinensis)是一种与灵长类动物关系密切的小型哺乳动物,是研究病毒和细菌感染的可行实验动物。在本研究中,我们对中国树鼩中的TLRs基因(tTLRs)进行了表征,并鉴定出13个假定的TLRs,它们是哺乳动物TLR1-TLR9、TLR11-TLR13的直系同源物,而TLR10在树鼩中是一个假基因。使用最大似然(ML)方法进行的正选择分析表明,tTLR8和tTLR9处于正选择之下,这可能与对病原体挑战的适应性有关。tTLRs的mRNA表达水平呈现出总体较低且具有组织特异性的模式,并且在丙型肝炎病毒(HCV)感染后显著上调。tTLR4和tTLR9发生了可变剪接,这导致了不同的转录本。系统发育分析和TLR结构预测表明,tTLRs在进化上是保守的,这可能反映了先天性免疫反应系统中的一种古老机制和结构。综上所述,TLRs在中国树鼩中既有保守特征也有独特特征。

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