Global transcriptome analysis in influenza-infected mouse lungs reveals the kinetics of innate and adaptive host immune responses.

Global transcriptome analysis in influenza-infected mouse lungs reveals the kinetics of innate and adaptive host immune responses.
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DOI:
10.1371/journal.pone.0041169
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Schughart K
Schughart K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pommerenke C;Wilk E;Srivastava B;Schulze A;Novoselova N;Geffers R;Schughart K

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感染是一个高度动态的过程,涉及宿主在许多层面上的复杂生物反应。为了在全球范围内描述这些过程,我们记录了在60天内用甲型流感病毒非致死性感染后小鼠肺部的基因表达变化。对大型数据集的全球分析确定了宿主反应的不同阶段。干扰素基因的增加和确定的NK特异性基因集的上调揭示了早期先天免疫应答阶段的开始。随后,可以通过T和B细胞特异性标记基因表达的增加观察到T和B细胞的浸润和活化。支气管相关淋巴组织的形成与B细胞基因表达和趋化因子亚群的改变有关。此外,我们比较了野生型小鼠和Rag2突变小鼠的基因表达谱。该分析容易地证明,Rag2突变体中T和B细胞应答的缺陷可以通过整个肺的整体基因表达模式的变化来检测。总之,我们的全面基因表达研究首次在转录组水平描述了急性甲型流感感染的整个宿主反应及其动力学。
An infection represents a highly dynamic process involving complex biological responses of the host at many levels. To describe such processes at a global level, we recorded gene expression changes in mouse lungs after a non-lethal infection with influenza A virus over a period of 60 days. Global analysis of the large data set identified distinct phases of the host response. The increase in interferon genes and up-regulation of a defined NK-specific gene set revealed the initiation of the early innate immune response phase. Subsequently, infiltration and activation of T and B cells could be observed by an augmentation of T and B cell specific signature gene expression. The changes in B cell gene expression and preceding chemokine subsets were associated with the formation of bronchus-associated lymphoid tissue. In addition, we compared the gene expression profiles from wild type mice with Rag2 mutant mice. This analysis readily demonstrated that the deficiency in the T and B cell responses in Rag2 mutants could be detected by changes in the global gene expression patterns of the whole lung. In conclusion, our comprehensive gene expression study describes for the first time the entire host response and its kinetics to an acute influenza A infection at the transcriptome level.
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