Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

eLife

Hyun Jae Lee¹  Pablo Soro-Barrio²  Claire Dunican³  Myrsini Kaforou³  Aubrey J Cunnington³  Athina Georgiadou³ 

[1] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia;Section of Paediatric Infectious Disease, Department of Infectious Disease, Imperial College London, London, United Kingdom;Section of Paediatric Infectious Disease, Department of Infectious Disease, Imperial College London, London, United Kingdom;Centre for Paediatrics and Child Health, Imperial College London, London, United Kingdom;

关键词: transcriptomics;    mouse models;    malaria;    Mouse;   

DOI  :  10.7554/eLife.70763

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY