Innate Immune Gene Transcript Level Associated with the Infection of Macrophages with Ectromelia Virus in Two Different Mouse Strains
Innate Immune Gene Transcript Level Associated with the Infection of Macrophages with Ectromelia Virus in Two Different Mouse Strains
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DOI：
10.1089/vim.2016.0173
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发表时间：
2017-06-01
期刊：
影响因子：
2.2
通讯作者：
Toka, Felix N.
中科院分区：
文献类型：
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作者：
Dolega, Patryk;Szulc-Dabrowska, Lidia;Toka, Felix N.
痘病毒已经进化出许多机制来避免受感染宿主的免疫应答，并且这些机制中的许多尚未完全描述。在这里，我们研究了先天性免疫基因的转录反应，BALB/c和C57 BL/6腹腔巨噬细胞感染后的莫斯科株鼠痘病毒（ECTV-Mos），目的是划定先天性免疫基因，有助于之间的差异易感性和耐药性致死性感染。我们显示了在抗病毒先天免疫受体、下游信号传导途径和应答组分的四类（Toll样受体信号传导、NOD样受体信号传导、RIG-I样受体信号传导和I型干扰素信号传导）中许多基因的普遍下调。会上提出了两项重要意见。首先，14个先天性抗病毒基因差异表达，在已知对ECTV-Mos感染具有抗性的C57 BL/6小鼠中发生2倍及以上的倍数变化上调，而相同的基因在BALB/c小鼠中下调，倍数变化为2倍及以下。第二，组织蛋白酶组基因在两种品系的小鼠中下调，但在C57 BL/6小鼠中，CtsL、CtsB和CtsS分别下调了17、38和62倍。我们发现，痘病毒深刻下调这三个组织蛋白酶的mRNA和蛋白质表达，这种变化似乎支持病毒复制。基于这些数据，我们建议，在基因表达的变化，观察可能有助于之间的差异，BALB/c和C57 BL/6小鼠的耐药/易感性致死感染ECTV-Mos。
Poxviruses have evolved numerous mechanisms to avoid the immune response of the infected host, and many of these mechanisms have not been fully described. Here, we studied the transcriptional response of innate immune genes in BALB/c and C57BL/6 peritoneal macrophages following infection with the Moscow strain of ectromelia virus (ECTV-Mos) with the aim of delineating innate immune genes that contribute to the difference between susceptibility and resistance to lethal infection. We show a generalized downregulation of many genes in four categories (toll-like receptor signaling, NOD-like receptor signaling, RIG-I-like receptor signaling, and type I interferon signaling) of antiviral innate immune receptors, downstream signaling pathways, and responsive components. Two important observations were made. First, 14 innate antiviral genes were differentially expressed with fold change upregulation of two and above occurring in C57BL/6 mice, known to be resistant to ECTV-Mos infection, whereas the same genes were downregulated in BALB/c mice with fold change of two and below. Second, the cathepsin group of genes was downregulated in both strains of mice but with profound fold changes of 17, 38, and 62 downregulation for CtsL, CtsB, and CtsS, respectively, in C57BL/6 mice. We show that a poxvirus profoundly downregulates both the mRNA and protein expression of these three cathepsins and this change appears to support virus replication. Based on these data we propose that the variations in gene expression observed may contribute to the difference in resistance/susceptibility between BALB/c and C57BL/6 mice to lethal infection by ECTV-Mos.