BACKGROUND Scrub typhus causes up to 35% mortality if left untreated. One billion people living in the endemic regions are at risk. In spite of its heavy disease burden in some of the most populated areas in the world, there is no vaccine available. Although the disease can be effectively treated by proper antibiotics, timely and accurate diagnosis remains a challenge. Orientia tsutsugamushi infects a variety of mammalian cells in vitro and replicates in the cytoplasm of the infected cells. Microarray analysis has been used extensively to study host-pathogen interactions in in vitro models to understand pathogenesis. However there is a lack of in vivo studies. RESULTS In this study, C3HeB/FeJ (C3H) mice were infected by O. tsutsugamushi via the intraperitoneal route and monitored gene expression at 10 different time points post infection. We observed two distinct types of expression profiles in the genes that we analyzed. There are two valleys (4-18 h and 2-4 days) with low number of differentially expressed genes (DEG) with three peaks with high number of DEG at 2 h, 1-day and 7-day post infection. Further analysis revealed that pathways like complement and coagulation cascade, and blood clotting cascade pathways showed significant global changes throughout entire time course. Real time quantitative Polymerase Chain Reaction (RT-qPCR) confirmed the change of expression for genes involved in complement and coagulation cascade. These results suggested dynamic regulation of the complement and coagulation cascades throughout most of the time post infection while some other specific pathways, such as fatty acid metabolism and tryptophan metabolism, are turned on or off at certain times post infection. CONCLUSIONS The findings highlight the complex interconnection among all different biological pathways. It is conceivable that specific pathways such as cell growth control and cell development in the host are affected by Orientia in the initial phase of infection for Orientia to grow intracellularly. Once Orientia is replicating successfully inside the host as infection progresses, the infection could activate pathways involved in cellular immune responses to defend for host cell survival and try to eliminate the pathogen.

中文翻译：

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东方感染C3HeB / FeJ小鼠中mRNA表达谱的时间分析。

背景技术如果不进行治疗，斑疹伤寒会导致高达35％的死亡率。生活在流行地区的十亿人处于危险之中。尽管在世界上一些人口最稠密的地区疾病负担很重，但没有可用的疫苗。尽管可以通过适当的抗生素有效治疗该疾病，但是及时准确的诊断仍然是一个挑战。ient虫东方虫在体外感染多种哺乳动物细胞，并在感染细胞的细胞质中复制。微阵列分析已被广泛用于研究体外模型中的宿主-病原体相互作用以了解发病机理。但是，缺乏体内研究。结果在这项研究中，C3HeB / FeJ（C3H）小鼠通过腹膜内途径被O虫O. tsutsugamushi感染，并在感染后10个不同时间点监测基因表达。我们在我们分析的基因中观察到两种不同类型的表达谱。在感染后2小时，1天和7天，有两个谷（4-18小时和2-4天），差异表达基因（DEG）的数量较少，三个峰值，而DEG的数量很高。进一步的分析表明，补体和凝血级联等途径以及凝血级联途径在整个时间过程中均显示出显着的整体变化。实时定量聚合酶链反应（RT-qPCR）证实了参与补体和凝血级联反应的基因表达的变化。这些结果表明，感染后大部分时间内动态调节补体和凝血级联反应，而其他一些特定途径，例如脂肪酸代谢和色氨酸代谢，在感染后的某些时间打开或关闭。结论研究结果突显了所有不同生物学途径之间的复杂相互联系。可以想象，在感染的初始阶段，宿主体内特定的途径（如细胞生长控制和宿主细胞发育）会受到Orientia的影响，Orientia才能在细胞内生长。一旦Orientia在感染过程中成功地在宿主体内复制，感染就可以激活细胞免疫反应中涉及的途径，以捍卫宿主细胞的存活并消除病原体。可以想象，在感染的初始阶段，宿主体内特定的途径（如细胞生长控制和宿主细胞发育）会受到Orientia的影响，Orientia才能在细胞内生长。一旦Orientia在感染过程中成功地在宿主体内复制，感染就可以激活细胞免疫反应中涉及的途径，以捍卫宿主细胞的存活并消除病原体。可以想象，在感染的初始阶段，宿主体内特定的途径（如细胞生长控制和宿主细胞发育）会受到Orientia的影响，Orientia才能在细胞内生长。一旦Orientia在感染过程中成功地在宿主体内复制，感染就可以激活细胞免疫反应中涉及的途径，以捍卫宿主细胞的存活并消除病原体。