A single-cell liver atlas of Plasmodium vivax infection

Cell Host Microbe. 2022 Jul 13;30(7):1048-1060.e5. doi: 10.1016/j.chom.2022.03.034. Epub 2022 Apr 19.


Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years and reactivate to cause recurrent blood-stage infection. Although they are an important target for malaria eradication, little is known about the molecular features of replicative and non-replicative intracellular liver-stage parasites and their host cell dependence. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites for transcriptional profiling. Coupling enrichment strategies with bulk and single-cell analyses, we capture both parasite and host transcripts in individual hepatocytes throughout the course of infection. We define host- and state-dependent transcriptional signatures and identify unappreciated populations of replicative and non-replicative parasites that share features with sexual transmissive forms. We find that infection suppresses the transcription of key hepatocyte function genes and elicits an anti-parasite innate immune response. Our work provides a foundation for understanding host-parasite interactions and reveals insights into the biology of P. vivax dormancy and transmission.

Keywords: MPCC; Plasmodium vivax; Seq-Well; dormancy; host-parasite interactions; hypnozoites; liver stage; single-cell; transcriptomics; transmission.

MeSH terms

  • Hepatocytes / parasitology
  • Humans
  • Liver / parasitology
  • Malaria* / parasitology
  • Malaria, Vivax* / parasitology
  • Plasmodium vivax / genetics