Liver malaria map paves the way for better treatments

By infecting humans, the malaria parasite first infiltrates the liver, where it undergoes a seven-day multiplication phase. This critical stage is a prime target for effective vaccines.

Leveraging advanced techniques, researchers at Stockholm University have crafted the inaugural comprehensive map of malaria infection in the mouse liver. Their findings, published in Nature Communications, hold promise for revolutionizing malaria treatment and vaccine development.

“By identifying the exact location of gene changes in liver tissue due to parasite infection, we can advance malaria research and find new drug and vaccine targets,” said Johan Ankarklev, study leader at Stockholm University.

This study, a testament to the power of collaboration, involved researchers from KTH, Karolinska Institute, NIH in the USA, and VIB in Belgium, all working together towards a common goal.

Using Spatial Transcriptomics and single-cell RNA sequencing, researchers mapped gene expression in malaria-infected mouse liver tissues. This technology captures gene expression across small regions and links it to specific tissue locations.

Merging this data helps identify cell types. Malaria, causing millions of infections and hundreds of thousands of deaths yearly, first develops silently in the liver before infecting blood cells.

The liver stage of malaria is a crucial target for vaccines, as only a few parasites reach and develop in the liver. This stage offers a chance for effective and long-lasting vaccines, but current vaccines have shown low effectiveness.

Johan Ankarklev highlights the crucial role of understanding the liver stage, and creating a detailed map of malaria infection in liver tissues helps fill this knowledge gap.

Researchers found that malaria parasites change gene expression in nearby host liver cells over time. Early in the infection, inflammation-related genes are activated.

Later, immune response genes are reduced, while genes for fatty acid metabolism increase, providing nutrients for parasite replication and reducing inflammation. This suggests parasites evade immune defenses and get nutrients by altering host cell genes.

Researchers found that injecting mosquito salivary gland lysate into control mice delayed immune response by over 12 hours, offering insights for future studies.

They also discovered “inflammatory hotspots” in the liver, areas with high cell density and immune activity, similar to those in viral infections. These hotspots may mark areas where the immune system successfully eliminates some malaria parasites.

Journal reference :

1. Hildebrandt, F., Iturritza, M.U., Zwicker, C. et al. Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution. Nature Communications. DOI:  10.1038/s41467-024-51418-2.