|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Mancio-Silva, L, Gural, N, Real, E, Wadsworth, MH, Butty, VL, March, S, Nerurkar, N, Hughes, TK, Roobsoong, W, Fleming, HE, Whittaker, CA, Levine, SS, Sattabongkot, J, Shalek, AK, Bhatia, SN|
|Journal||Cell Host Microbe|
|Date Published||2022 Apr 13|
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.
|Alternate Journal||Cell Host Microbe|