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

机译:干扰素λ调控基因在鸡原代成纤维细胞和免疫器官中的动态表达

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摘要

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.
机译:干扰素(IFN)是多效性细胞因子,可建立抵御脊椎动物病毒感染的第一道防线。已经鉴定出几种类型的IFN。但是,在家禽中可获得的信息有限,尤其是使用活体动物实验模型时。最近显示,IFN-λ(IFN-λ)对哺乳动物的病毒病原体具有重要的抗病毒作用。为了研究鸡IFN-λ(chIFN-λ)作为先天免疫调节剂的体内潜力以及潜在的抗病毒治疗剂,我们对chIFN-λ刺激的鸡免疫器官(体内)的转录组进行了分析,并对其进行了比较。与原代鸡胚成纤维细胞结合(体外)。利用杆状病毒表达载体系统(BEVS),制备了重组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的IFN调控基因。使用Fabricous和胸腺的法氏囊的RNA-seq转录谱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)证明了关键免疫基因(毒蛇毒素,IKKB,CCL5,IL1β和AP1)的上调以及抗病毒信号通路。有趣的是,该实验方法揭示了在体内和体外模型中chIFN-λ抗病毒潜力的对比证据。综上所述,我们的数据表明chIFN-λ作为有效的抗病毒细胞因子的潜力,并强调了其在家禽中作为抗病毒治疗剂的未来用途。

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