Genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how Burkholderia pseudomallei overcomes host innate immunity.
Genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how Burkholderia pseudomallei overcomes host innate immunity.
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DOI：
10.1186/1471-2164-11-672
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发表时间：
2010-11-27
期刊：
影响因子：
4.4
通讯作者：
Nathan S
中科院分区：
文献类型：
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作者：
Chin CY;Monack DM;Nathan S
目前，人们对类鼻疽伯克霍尔德氏菌（B.假鼻疽）与其宿主相互作用以引起类鼻疽病症状。我们建立了一个小鼠急性期类鼻疽模型，并使用DNA微阵列技术来研究全球宿主/病原体相互作用。我们在42小时的感染期内比较了感染的肝脏和脾脏与未感染组织的转录组，以确定其表达在急性感染中发生变化的基因。活菌B。在42小时的感染过程中，在血液、肝脏和脾脏中始终检测到假鼻疽细胞。在此时间过程中的肝脏和脾脏的微阵列分析表明，参与免疫反应，应激反应，细胞周期调控，蛋白酶体降解，细胞代谢和信号转导途径的基因差异调节。Toll样受体2（TLR 2）基因表达的上调表明，TLR 2介导的信号通路负责识别和启动急性B的炎症反应。类鼻疽感染。大多数高度升高的炎症基因是一组在一般炎症感染中常见的“核心宿主免疫反应”基因。伴随着这种最初的炎症反应，我们观察到与细胞死亡，半胱天冬酶激活和肽水解相关的转录物的增加，最终促进宿主的组织损伤。负责恢复宿主细胞稳态和消除细胞内细菌的补体系统仅在感染后24小时被激活。然而，在这个时间点，多种宿主营养代谢和细胞途径，包括糖酵解，脂肪酸代谢和三羧酸（TCA）循环受到抑制。急性类鼻疽期间宿主转录反应的详细图片突出了24小时内在宿主中激活的广泛的先天免疫机制，包括在一般炎症感染中常见的核心免疫反应。然而，这种激活在感染后42小时被抑制，此外，下游补体系统的次优激活和功能促进细菌的不受控制的传播。
At present, very little is known about how Burkholderia pseudomallei (B. pseudomallei) interacts with its host to elicit melioidosis symptoms. We established a murine acute-phase melioidosis model and used DNA microarray technology to investigate the global host/pathogen interaction. We compared the transcriptome of infected liver and spleen with uninfected tissues over an infection period of 42 hr to identify genes whose expression is altered in response to an acute infection. Viable B. pseudomallei cells were consistently detected in the blood, liver and spleen during the 42 hr course of infection. Microarray analysis of the liver and spleen over this time course demonstrated that genes involved in immune response, stress response, cell cycle regulation, proteasomal degradation, cellular metabolism and signal transduction pathways were differentially regulated. Up regulation of toll-like receptor 2 (TLR2) gene expression suggested that a TLR2-mediated signalling pathway is responsible for recognition and initiation of an inflammatory response to the acute B. pseudomallei infection. Most of the highly elevated inflammatory genes are a cohort of "core host immune response" genes commonly seen in general inflammation infections. Concomitant to this initial inflammatory response, we observed an increase in transcripts associated with cell-death, caspase activation and peptidoglysis that ultimately promote tissue injury in the host. The complement system responsible for restoring host cellular homeostasis and eliminating intracellular bacteria was activated only after 24 hr post-infection. However, at this time point, diverse host nutrient metabolic and cellular pathways including glycolysis, fatty acid metabolism and tricarboxylic acid (TCA) cycle were repressed. This detailed picture of the host transcriptional response during acute melioidosis highlights a broad range of innate immune mechanisms that are activated in the host within 24 hrs, including the core immune response commonly seen in general inflammatory infections. Nevertheless, this activation is suppressed at 42 hr post-infection and in addition, suboptimal activation and function of the downstream complement system promotes uncontrolled spread of the bacteria.
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DOI：
10.1016/j.diagmicrobio.2007.01.002
发表时间：
2007-07-01
影响因子：
2.9
作者：
Lee, Song-Hua;Chong, Chan-Eng;Nathan, Sheila
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影响因子：
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发表时间：
1998-01-01
影响因子：
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影响因子：
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作者：
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