Single-Cell Atlas of Malaria at Liver-Stage of Infection Identifies Key Gene Expression Programs

A single-cell atlas of the malaria-causing Plasmodium parasite at the point it has infected host liver cells is presented in Nature this week, offering molecular insights that could help in combating the disease. Malaria infection involves an obligatory, yet clinically silent liver stage. Previous ex vivo studies have suggested that the pace of Plasmodium infection at this point varies between different types of hepatocytes, but accounting for the hepatocyte spatial heterogeneity and identifying heterogeneous host and parasite responses requires in vivo single-cell approaches. To that end, a team led by Weizmann Institute of Science researchers combined single-cell RNA sequencing and single-molecule transcript imaging to characterize host and parasite temporal gene expression programs in the livers of Plasmodium-infected mice. They identified several potentially adaptive programs of the host hepatocyte and the parasite, including processes such as iron and fatty acid metabolism, as well as zonal trends in both the host and the parasite. "Our atlas can serve as a basis for future exploration of potential vulnerabilities and the identification of targetable host and parasite pathways," the study's authors write.