Cell Host & Microbe
Volume 30, Issue 7, 13 July 2022, Pages 1048-1060.e5
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A single-cell liver atlas of Plasmodium vivax infection

https://doi.org/10.1016/j.chom.2022.03.034Get rights and content
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Highlights

  • MPCC and Seq-Well platforms enable single-cell survey of P. vivax liver infection

  • Dual transcriptome analysis links dormancy and sexual conversion to host state

  • Single-cell profiling reveals dynamic host responses in infected and bystander cells

  • Dataset is validated via in situ transcript detection and functional assays

Summary

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

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

Data and code availability

Bulk RNA-seq and scRNA-seq data have been deposited at GEO (GSE197459). Gene-by-cell expression matrices have been deposited at Zenodo (doi:zenodo.6280956). Any additional information required to reanalyze the data reported in this paper will be available from the lead contact upon request. Microscopy data reported in this paper will be shared by the lead contact upon request.

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11

These authors contributed equally

12

Lead contact