Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.
Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.
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DOI：
10.7554/elife.70763
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发表时间：
2022-01-10
期刊：
影响因子：
7.7
通讯作者：
Cunnington AJ
中科院分区：
文献类型：
--
作者：
Georgiadou A;Dunican C;Soro-Barrio P;Lee HJ;Kaforou M;Cunnington AJ
最近的倡议，以改善翻译的结果从动物模型到人类疾病的重点是可重复性，但量化的相关性动物模型仍然是一个挑战。在这里，我们使用比较转录组学的血液，以评估系统的主机之间的响应和一致性与不同的临床表现的疟疾和五种常用的小鼠模型的人类。约氏疟原虫17XL感染小鼠最接近地再现了在主要的人类严重疟疾综合征中所见的基因表达变化的概况，伴随着高寄生虫生物量、严重贫血、高乳酸血症和脑微血管病理。然而，也有相当大的不一致性，在不同的宿主物种之间的基因表达的变化，并在所有的模型，这表明在每个模型中的相关性的生物学机制进行实验之前，应进行评估。这些数据将有助于选择适当的模型转化疟疾研究，该方法是推广到其他疾病模型。
Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here, we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between the different host species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. These data will aid the selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.