Host cell maturation modulates parasite invasion and sexual differentiation in Plasmodium berghei

Hentzschel, F., Gibbins, M. P. , Attipa, C., Beraldi, D., Moxon, C. A. , Otto, T. D. and Marti, M. (2022) Host cell maturation modulates parasite invasion and sexual differentiation in Plasmodium berghei. Science Advances, 8(17), eabm7348. (doi: 10.1126/sciadv.abm7348)

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Abstract

Malaria remains a global health problem causing more than 400,000 deaths annually. Plasmodium parasites, the causative agents of malaria, replicate asexually in red blood cells (RBCs) of their vertebrate host, while a subset differentiates into sexual stages (gametocytes) for mosquito transmission. Parasite replication and gametocyte maturation in the erythropoietic niches of the bone marrow and spleen contribute to pathogenesis and drive transmission, but the mechanisms underlying this organ enrichment remain unknown. Here, we performed a comprehensive analysis of rodent P. berghei infection by flow cytometry and single-cell RNA sequencing. We identified CD71 as a host receptor for reticulocyte invasion and found that parasites metabolically adapt to the host cell environment. Transcriptional analysis and functional assays further revealed a nutrient-dependent tropism for gametocyte formation in reticulocytes. Together, we provide a thorough characterization of host-parasite interactions in erythropoietic niches and define host cell maturation state as the key driver of parasite adaptation.

Item Type:Articles
Additional Information:Funding: This work was supported by Deutsche Forschungsgemeinschaft 404044656 (to F.H.), Wolfson Merit Royal Society Award (to M.M.), Wellcome Trust Investigator award 110166 (to F.H., M.P.G., and M.M.), Wellcome Trust Center award 104111 (to F.H., M.P.G., C.A.M., T.D.O., and M.M.), ERC Consolidator Award BoneMalar (to F.H. and M.M.), and Wellcome Trust 204820/Z/16/Z (to T.D.O.)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Moxon, Dr Christopher and Gibbins, Dr Matt and Otto, Dr Thomas and Hentzschel, Dr Franziska and Marti, Professor Matthias and Beraldi, Dr Dario
Authors: Hentzschel, F., Gibbins, M. P., Attipa, C., Beraldi, D., Moxon, C. A., Otto, T. D., and Marti, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
Published Online:27 April 2022
Copyright Holders:Copyright © The Author(s) 2022
First Published:First published in Science Advances 8(17): eabm7348
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172862Elucidating mechanisms of extracellular vesiclemediated cellular communication and stage conversion in malaria parasites.Matthias MartiWellcome Trust (WELLCOTR)110166/Z/15/ZIII - Parasitology
171824Characterization of Toxoplasma gondii interaction with the human host cell and Host-Parasite co-evolution: Toxoplasma gondii as a case studyMusa HassanWellcome Trust (WELLCOTR)104111/B/14/ZIII - Parasitology
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences