A single-cell liver atlas of Plasmodium vivax infection

Biology Biology
Cell Atlas Cell Atlas
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Microbiology Microbiology
Technology Technology
Alex K. Shalek Alex K. Shalek
Marc Wadsworth II Marc Wadsworth II
Travis Hughes Travis Hughes

Mancio-Silva et al.▾ Mancio-Silva, L.*, Gural, N.*, Real, E., Wadsworth II, M.H., Butty, V.L., March, S., Nerurkar, N., Hughes, T.K., Roobsoong, W., Fleming, H.E., Whittaker, C.A., Levine, S.S., Sattabongkot, J., Shalek, A.K., Bhatia, S.N.

Cell Host & Microbe , Volume 30

April, 2022


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.