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

Area of Science:

• Comparative transcriptomics
• Translational research
• Infectious disease modeling

Background:

• Improving the translation of animal model findings to human disease is crucial.
• Quantifying the relevance of animal models for human diseases remains a significant challenge.
• Comparative transcriptomics offers a method to evaluate host responses across species.

Purpose of the Study:

• To evaluate the systemic host response and its concordance between humans with malaria and commonly used mouse models.
• To identify which mouse models best reflect human malaria transcriptomic profiles.
• To provide data to aid in selecting appropriate models for translational malaria research.

Main Methods:

• Comparative transcriptomics of blood samples from humans with malaria and five mouse models.
• Analysis of gene expression profiles to assess systemic host response.
• Correlation of transcriptomic data with clinical manifestations of severe malaria.

Main Results:

• Plasmodium yoelii 17XL infection in mice most closely reproduced the gene expression profile of severe human malaria syndromes.
• This model also exhibited high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology.
• Significant discordance in gene expression changes was observed between human and mouse models, and across different mouse models.

Conclusions:

• Plasmodium yoelii 17XL mouse model shows high relevance for severe malaria transcriptomic studies.
• The study underscores the necessity of assessing model-specific biological relevance before experimental use.
• The comparative transcriptomics approach is generalizable to other disease modeling efforts.