Host cell maturation modulates parasite invasion and sexual differentiation in <i>Plasmodium berghei</i>

Hentzschel, Franziska, Gibbins, Matthew P, Attipa, Charalampos ORCID: 0000-0001-6039-6586, Beraldi, Dario, Moxon, Christopher A, Otto, Thomas D and Marti, Matthias
(2022) Host cell maturation modulates parasite invasion and sexual differentiation in <i>Plasmodium berghei</i>. SCIENCE ADVANCES, 8 (17). eabm7348-.

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Malaria remains a global health problem causing more than 400,000 deaths annually. <i>Plasmodium</i> 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 <i>P. berghei</i> 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: Article
Uncontrolled Keywords: Animals, Culicidae, Parasites, Plasmodium berghei, Malaria, Sex Differentiation
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 12 Oct 2022 09:22
Last Modified: 19 Oct 2023 09:24
DOI: 10.1126/sciadv.abm7348
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