In:
Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-08-02)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-023-40298-7
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2553671-0
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