Zonal human hepatocytes are differentially permissive to Plasmodium falciparum malaria parasites
Open Access
- 18 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 40 (6), e106583
- https://doi.org/10.15252/embj.2020106583
Abstract
Plasmodium falciparum (Pf) is a major cause of human malaria and is transmitted by infected Anopheles mosquitoes. The initial asymptomatic infection is characterized by parasite invasion of hepatocytes, followed by massive replication generating schizonts with blood‐infective merozoites. Hepatocytes can be categorized by their zonal location and metabolic functions within a liver lobule. To understand specific host conditions that affect infectivity, we studied Pf parasite liver stage development in relation to the metabolic heterogeneity of fresh human hepatocytes. We found selective preference of different Pf strains for a minority of hepatocytes, which are characterized by the particular presence of glutamine synthetase (hGS). Schizont growth is significantly enhanced by hGS uptake early in development, showcasing a novel import system. In conclusion, Pf development is strongly determined by the differential metabolic status in hepatocyte subtypes. These findings underscore the importance of detailed understanding of hepatocyte host‐Pf interactions and may delineate novel pathways for intervention strategies.Funding Information
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.192.171)
- H2020 European Research Council (ERC‐2014‐StG 639776)
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