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

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.

Automated summary

Recent research has focused on improving the translation of animal models to human disease, but determining the relevance of animal models remains a challenge. In this study, comparative transcriptomics were used to evaluate the systemic host response in humans with different clinical manifestations of malaria and commonly used mouse models. The results showed that the Plasmodium yoelii 17XL infection model in mice closely reproduced the gene expression changes seen in severe malaria in humans. However, there was also significant discordance in gene expression changes between different host species and models.