Modulation of activation-associated host cell gene expression by the apicomplexan parasite Theileria annulata
Modulation of activation-associated host cell gene expression by the apicomplexan parasite Theileria annulata
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DOI：
10.1111/j.1462-5822.2012.01809.x
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发表时间：
2012-09-01
影响因子：
3.4
通讯作者：
Shiels, Brian
中科院分区：
文献类型：
--
作者：
Durrani, Zeeshan;Weir, William;Shiels, Brian
牛白细胞被环形泰勒虫感染导致转化的感染细胞的建立。已知宿主细胞的感染促进促炎性转录因子的组成型激活，所述促炎性转录因子具有有益或有害的潜力。在这项研究中，我们比较了LPS激活对未感染的牛白细胞（BL 20细胞）和它们的泰勒虫感染的对应物（TBL 20）的影响。还比较了代表活化的未感染的BL 20相对于TBL 20细胞的基因表达谱。结果表明，长时间的LPS刺激诱导细胞死亡和NF-？B在BL 20细胞中，泰勒虫感染的细胞的活力不受影响。基因表达网络的分析提供的证据表明，寄生虫建立严格的控制与细胞活化的途径，通过调节接收外部刺激，并通过显着改变感染激活的转录因子靶向基因的表达结果。数据集的途径分析鉴定了参与操纵与感染的转化细胞相关的细胞功能的新候选基因。数据表明，T.？环状寄生虫可以不可逆地重新配置与炎性疾病和癌症的发展相关的宿主细胞基因表达网络，以产生有益于受感染白细胞的存活和繁殖的结果。
Infection of bovine leucocytes by Theileria annulata results in establishment of transformed, infected cells. Infection of the host cell is known to promote constitutive activation of pro-inflammatory transcription factors that have the potential to be beneficial or detrimental. In this study we have compared the effect of LPS activation on uninfected bovine leucocytes (BL20 cells) and their Theileria-infected counterpart (TBL20). Gene expression profiles representing activated uninfected BL20 relative to TBL20 cells were also compared. The results show that while prolonged stimulation with LPS induces cell death and activation of NF-?B in BL20 cells, the viability of Theileria-infected cells was unaffected. Analysis of gene expression networks provided evidence that the parasite establishes tight control over pathways associated with cellular activation by modulating reception of extrinsic stimuli and by significantly altering the expression outcome of genes targeted by infection-activated transcription factors. Pathway analysis of the data set identified novel candidate genes involved in manipulation of cellular functions associated with the infected transformed cell. The data indicate that the T.?annulata parasite can irreversibly reconfigure host cell gene expression networks associated with development of inflammatory disease and cancer to generate an outcome thatis beneficial to survival and propagation of the infected leucocyte.