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干扰素 λ 调节基因在鸡原代成纤维细胞和免疫器官中的动态表达。

Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken.

机构信息

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Division of Biomedical and Life sciences, Faculty of Health and Medicine, Lancaster University,LA1 4YG, Lancaster, UK.

出版信息

Genes (Basel). 2019 Feb 14;10(2):145. doi: 10.3390/genes10020145.

Abstract

Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry.

摘要

干扰素 (IFNs) 是一类多功能细胞因子,在脊椎动物中构成了抵御病毒感染的第一道防线。已经鉴定出几种类型的 IFN,但在禽类中,特别是在活体动物实验模型中,可用的信息有限。IFN-λ (IFN-λ) 最近被证明在哺乳动物中对病毒病原体具有显著的抗病毒作用。为了研究鸡 IFN-λ (chIFN-λ) 作为先天免疫调节剂和潜在抗病毒治疗剂的体内潜力,我们对 chIFN-λ 刺激的鸡免疫器官(体内)进行了转录组分析,并将其与原代鸡胚胎成纤维细胞(体外)进行了比较。利用杆状病毒表达载体系统 (BEVS) ,生产了重组 chIFN-λ3 (rchIFN-λ3) ,并证明了其生物学活性。rchIFNλ3 在原代鸡成纤维细胞中诱导了大量 IFN 调节基因的表达。使用 RNA-seq 进行的转录组分析和随后的生物信息学分析(基因本体论、差异表达基因和 KEGGs 分析)表明,法氏囊和胸腺中的关键免疫基因(viperin、IKKB、CCL5、IL1β 和 AP1)以及抗病毒信号通路均上调。有趣的是,这种实验方法在体内和体外模型中均揭示了 chIFN-λ 抗病毒潜力的相互矛盾的证据。总之,我们的数据表明 chIFN-λ 作为一种有效的抗病毒细胞因子的潜力,并强调了其在禽类中作为抗病毒治疗剂的未来可能用途。

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