Single-cell RNA profiling of Plasmodium vivax-infected hepatocytes reveals parasite- and host- specific transcriptomic signatures and therapeutic targets

In humans, malaria-causing Plasmodium parasites invade and replicate in the liver before mounting an infection in the blood. A few Plasmodium species, including P. vivax, can cause relapsing infections due to forms that persist in the liver known as hypnozoites. While interventions targeting the hypnozoite can prevent clinical malaria, little is known about their biology at the molecular level. Transcriptome-wide assessment of individual hypnozoites has not been accessible due to the technical challenges associated with liver stage infections. To overcome technical limitations, we performed single-cell transcriptional profiling of liver stages generated using an in vitro infection platform. In elucidating the transcriptional signatures of P. vivax liver forms, as well as hepatocytes in response to infection, our data provide new insights into these host-parasite interactions. An improved understanding of these interactions will allow for novel drug or vaccine interventions targeting either parasite- or hepatocyte- specific metabolic pathways essential for successful liver stage development and disease progression.