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Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures

Author

Listed:
  • Annie S. P. Yang

    (Radboud University Medical Center)

  • Devanjali Dutta

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    Merus)

  • Kai Kretzschmar

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    University Hospital Würzburg)

  • Delilah Hendriks

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute)

  • Jens Puschhof

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    German Cancer Research Center (DKFZ))

  • Huili Hu

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    Shandong University)

  • Kim E. Boonekamp

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    German Cancer Research Center (DKFZ))

  • Youri Waardenburg

    (Radboud University Medical Center)

  • Susana M. Chuva de Sousa Lopes

    (Leiden University Medical Center)

  • Geert-Jan Gemert

    (Radboud University Medical Center)

  • Johannes H. W. Wilt

    (Radboud University Medical Center)

  • Teun Bousema

    (Radboud University Medical Center)

  • Hans Clevers

    (Royal Netherlands Academy of Arts and Sciences
    Oncode Institute
    Princess Maxima Center (PMC) for Pediatric Oncology
    Pharma, Research and Early Development (pRED) of F. Hoffmann-La Roche Ltd)

  • Robert W. Sauerwein

    (Radboud University Medical Center
    TropIQ Health Sciences)

Abstract

Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.

Suggested Citation

  • Annie S. P. Yang & Devanjali Dutta & Kai Kretzschmar & Delilah Hendriks & Jens Puschhof & Huili Hu & Kim E. Boonekamp & Youri Waardenburg & Susana M. Chuva de Sousa Lopes & Geert-Jan Gemert & Johannes, 2023. "Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40298-7
    DOI: 10.1038/s41467-023-40298-7
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    References listed on IDEAS

    as
    1. Alison Roth & Steven P. Maher & Amy J. Conway & Ratawan Ubalee & Victor Chaumeau & Chiara Andolina & Stephen A. Kaba & Amélie Vantaux & Malina A. Bakowski & Richard Thomson-Luque & Swamy Rakesh Adapa , 2018. "Author Correction: A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    2. Alison Roth & Steven P. Maher & Amy J. Conway & Ratawan Ubalee & Victor Chaumeau & Chiara Andolina & Stephen A. Kaba & Amélie Vantaux & Malina A. Bakowski & Richard Thomson-Luque & Swamy Rakesh Adapa , 2018. "A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
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