A single-cell liver atlas of Plasmodium vivax infection
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Cell host & microbe - 30(2022), 7 vom: 13. Juli, Seite 1048-1060.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mancio-Silva, Liliana [VerfasserIn] |
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| Links: |
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| Themen: |
Dormancy |
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| Anmerkungen: |
Date Completed 18.07.2022 Date Revised 20.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.chom.2022.03.034 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Nerurkar, Niketa |e verfasserin |4 aut | |
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| 700 | 1 | |a Roobsoong, Wanlapa |e verfasserin |4 aut | |
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| 700 | 1 | |a Whittaker, Charlie A |e verfasserin |4 aut | |
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| 700 | 1 | |a Shalek, Alex K |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatia, Sangeeta N |e verfasserin |4 aut | |
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