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

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 H. W. Wilt, Teun Bousema, Hans Clevers () and Robert W. Sauerwein ()
Additional contact information
Annie S. P. Yang: Radboud University Medical Center
Devanjali Dutta: Royal Netherlands Academy of Arts and Sciences
Kai Kretzschmar: Royal Netherlands Academy of Arts and Sciences
Delilah Hendriks: Royal Netherlands Academy of Arts and Sciences
Jens Puschhof: Royal Netherlands Academy of Arts and Sciences
Huili Hu: Royal Netherlands Academy of Arts and Sciences
Kim E. Boonekamp: Royal Netherlands Academy of Arts and Sciences
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
Robert W. Sauerwein: Radboud University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40298-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40298-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40298-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().