Whole genome response in guinea pigs infected with the high virulence strain Mycobacterium tuberculosis TT372.
Whole genome response in guinea pigs infected with the high virulence strain Mycobacterium tuberculosis TT372.
复制标题
DOI：
10.1016/j.tube.2014.10.001
复制
发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Orme IM
中科院分区：
文献类型：
--
作者：
Aiyaz M;Bipin C;Pantulwar V;Mugasimangalam R;Shanley CA;Ordway DJ;Orme IM
在这项研究中，我们进行了一个基于微阵列的全基因组分析的基因表达后，豚鼠暴露于低剂量的非典型北京西开普省的结核分枝杆菌TT 372株气溶胶，收获肺组织后，感染后三周的时间，效应免疫开始达到高峰。感染导致此时多个基因的非常大的上调，特别是在肺中的“趋化因子风暴”的背景下。在两个月前接种BCG的动物中，总体基因表达显著降低，但在这两种情况下，观察到以γ干扰素[IFNγ]和肿瘤坏死因子[TNFα]为特征的强烈特征，表明这些动物中存在强效TH 1应答。尽管它们的作用直到感染后期才被观察到，但即使在这个早期时间点，也观察到与调节性T细胞的潜在出现相关的基因表达模式。涉及肺修复、氧化应激反应和细胞运输的基因强烈表达，但有趣的是，这些基因模式在感染和接种疫苗/感染的动物组之间有很大差异。考虑到该物种作为结核病相关且具有成本效益的小动物模型的重要性，这种方法有可能提供关于疫苗接种对疾病过程控制的影响的新信息。
In this study we conducted a microarray-based whole genomic analysis of gene expression in the lungs after exposure of guinea pigs to a low dose aerosol of the Atypical Beijing Western Cape TT372 strain of Mycobacterium tuberculosis, after harvesting lung tissues three weeks after infection at a time that effector immunity is starting to peak. The infection resulted in a very large up-regulation of multiple genes at this time, particularly in the context of a “chemokine storm” in the lungs. Overall gene expression was considerably reduced in animals that had been vaccinated with BCG two months earlier, but in both cases strong signatures featuring gamma interferon [IFNγ] and tumor necrosis factor [TNFα] were observed indicating the potent TH1 response in these animals. Even though their effects are not seen until later in the infection, even at this early time point gene expression patterns associated with the potential emergence of regulatory T cells were observed. Genes involving lung repair, response to oxidative stress, and cell trafficking were strongly expressed, but interesting these gene patterns differed substantially between the infected and vaccinated/infected groups of animals. Given the importance of this species as a relevant and cost-effective small animal model of tuberculosis, this approach has the potential to provide new information regarding the effects of vaccination on control of the disease process.
登录
查看更多内容
影响因子：
5.8
作者：
Mollenkopf, HJ;Hahnke, K;Kaufmann, SHE
通讯作者：
Kaufmann, SHE
DOI：
10.1007/978-1-4614-6111-1_9
发表时间：
2013-01-01
期刊：
NEW PARADIGM OF IMMUNITY TO TUBERCULOSIS
影响因子：
--
作者：
Larson, Ryan P.;Shafiani, Shahin;Urdahl, Kevin B.
通讯作者：
Urdahl, Kevin B.
影响因子：
5.5
作者：
Shang, Shaobin;Shanley, Crystal A.;Basaraba, Randall J.
通讯作者：
Basaraba, Randall J.
影响因子：
82.9
作者：
Gagliani, Nicola;Magnani, Chiara F.;Roncarolo, Maria-Grazia
通讯作者：
Roncarolo, Maria-Grazia
影响因子：
3.2
作者：
Basaraba, Randall J.;Dailey, Deanna D.;Orme, Ian M.
通讯作者：
Orme, Ian M.