A single-cell liver atlas of Plasmodium vivax infection
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1-s2.0-S1931312822001640-main.pdf
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Published version
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4.21 MB
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Author(s) • • • • • • • • •
Mancio-Silva, Liliana
Gural, Nil
Real, Eliana
Wadsworth, Marc H
Butty, Vincent L
March, Sandra
Nerurkar, Niketa
Hughes, Travis K
Roobsoong, Wanlapa
Fleming, Heather E
Date Issued
April 2022
Journal
Cell Host & Microbe
Publisher
Elsevier BV
Citation
Mancio-Silva, Liliana, Gural, Nil, Real, Eliana, Wadsworth, Marc H, Butty, Vincent L et al. 2022. "A single-cell liver atlas of Plasmodium vivax infection." Cell Host & Microbe.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemistry
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/j.chom.2022.03.034