An in-depth comparison of the porcine, murine arid human inflammasomes; lessons from the porcine genome and transcriptome
An in-depth comparison of the porcine, murine arid human inflammasomes; lessons from the porcine genome and transcriptome
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DOI：
10.1016/j.vetmic.2016.05.013
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发表时间：
2017-04-01
影响因子：
3.3
通讯作者：
Urban, Joseph F., Jr.
中科院分区：
文献类型：
--
作者：
Dawson, Harry D.;Smith, Allen D.;Urban, Joseph F., Jr.
新出现的证据表明，猪是一种科学上可以接受的介于啮齿动物和人类之间的中间物种，可以用来模拟与人类相关的免疫功能。最近已经对猪基因组进行了测序，并发表了对猪免疫组体的几个初步结构和功能分析。在这里，我们提供了一种扩展的电子分析方法，使用改进的猪转录组组装，提供了与炎症体、对Toll样受体配体的反应以及M1巨噬细胞极化相关的基因的深入分析，并以大肠杆菌为模式生物。对同源基因家族的扩展或收缩的比较表明，人类和猪的基因比率和基因类别比小鼠的更相似；然而，发现了几个新的猪或偶蹄目动物特有的旁系基因或伪基因。同源性和结构基序的保守性表明，猪与人类蛋白质的总体相似性明显高于小鼠。尽管有这些相似之处，但在猪中发现了四个典型的炎症体通路中的两个，在黑色素瘤2(AIM2)和NLR家族和包含4的卡片域(NLRC4)中缺失。通过转录组，使用下一代测序方法，评估了猪M1 M phi对干扰素-γ(IFN-γ)和脂多糖(LPS)的反应。我们的分析显示主要是类似人类的反应，但也观察到了一些类似老鼠的反应，以及许多猪或偶蹄目动物特有的基因的诱导。这项工作支持使用猪来模拟人类对感染的免疫和炎症反应。然而，必须谨慎行事，因为猪在几个基本途径上与人类不同。爱思唯尔出版公司(Elsevier B.V.)
Emerging evidence suggests that swine are a scientifically acceptable intermediate species between rodents and humans to model immune function relevant to humans. The swine genome has recently been sequenced and several preliminary structural and functional analysis of the porcine immunome have been published. Herein we provide an expanded in silico analysis using an improved assembly of the porcine transcriptome that provides an in depth analysis of genes that are related to inflammasomes, responses to Toll-like receptor ligands, and M1 macrophage polarization and Escherichia colt as a model organism. Comparisons of the expansion or contraction of orthologous gene families indicated more similar rates and classes of genes in humans and pigs than in mice; however several novel porcine or artiodactyl-specific paralogs or pseudogenes were identified. Conservation of homology and structural motifs of orthologs revealed that the overall similarity to human proteins was significantly higher for pigs compared to mouse. Despite these similarities, two out of four canonical inflammasome pathways, Absent in melanoma 2 (AIM2) and NLR family and CARD domain containing 4 (NLRC4), were found to be missing in pigs. Pig M1 M phi polarization in response to interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) was assessed, via the transcriptome, using next generation sequencing. Our analysis revealed predominantly human-like responses however some, mouse-like responses were observed, as well as induction of numerous pig or artiodactyl-specific genes. This work supports using swine to model both human immunological and inflammatory responses to infection. However, caution must be exercised as pigs differ from humans in several fundamental pathways. Published by Elsevier B.V.