Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution

Area of Science:

• Parasitology
• Immunology
• Genomics

Background:

• The liver stage of malaria parasite Plasmodium infection is clinically silent but involves massive parasite replication.
• Understanding host responses in the liver tissue during malaria is crucial for developing interventions.

Purpose of the Study:

• To delineate host-pathogen interactions in Plasmodium berghei-infected liver tissues using spatial transcriptomics and single-nuclei RNA sequencing.
• To explore the coordination of host responses across liver tissue during malaria infection.

Main Methods:

• Spatial transcriptomics and single-nuclei RNA sequencing were performed on Plasmodium berghei-infected mouse liver tissues over multiple time points.
• Gene expression changes and cellular responses were analyzed in infected and control tissues.

Main Results:

• Significant spatial gene expression changes were observed, including alterations in lipid metabolism near Plasmodium infection sites.
• Distinct inflammation programs and "inflammatory hotspots" enriched with specific immune cells were identified across liver lobules.
• Upregulation of inflammatory genes was noted in control liver tissues exposed to mosquito salivary gland components, but with a delayed response compared to parasite infection.

Conclusions:

• This study provides a benchmark for investigating tissue-level host-parasite interactions and informs in vivo study design for malaria research.
• The findings offer insights into host immune responses during the silent liver stage of malaria and potential targets for intervention strategies.