title: Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes.
abstract: Plasmodium vivax merozoites only invade reticulocytes, a minor though heterogeneous population of red blood cell precursors that can be graded by levels of transferrin receptor (CD71) expression. The development of a protocol that allows sorting reticulocytes into defined developmental stages and a robust ex vivo P vivax invasion assay has made it possible for the first time to investigate the fine-scale invasion preference of P vivax merozoites. Surprisingly, it was the immature reticulocytes (CD71(+)) that are generally restricted to the bone marrow that were preferentially invaded, whereas older reticulocytes (CD71(-)), principally found in the peripheral blood, were rarely invaded. Invasion assays based on the CD71(+) reticulocyte fraction revealed substantial postinvasion modification. Thus, 3 to 6 hours after invasion, the initially biomechanically rigid CD71(+) reticulocytes convert into a highly deformable CD71(-) infected red blood cell devoid of host reticular matter, a process that normally spans 24 hours for uninfected reticulocytes. Concurrent with these changes, clathrin pits disappear by 3 hours postinvasion, replaced by distinctive caveolae nanostructures. These 2 hitherto unsuspected features of P vivax invasion, a narrow preference for immature reticulocytes and a rapid remodeling of the host cell, provide important insights pertinent to the pathobiology of the P vivax infection.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Department of Biomedical Engineering and Mechanobiology Institute, and.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore;
authors.forename: Rou
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore;
authors.forename: Kevin S W
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Rossarin
authors.initials: R
authors.lastname: Suwanarusk
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore;
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Cho
authors.affiliation: Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore;
authors.forename: Esther Geok Liang
authors.initials: EG
authors.lastname: Koh
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Cindy S
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand;
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore;
authors.forename: Mah Lee
authors.initials: ML
authors.lastname: Ng
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.affiliation: Department of Biomedical Engineering and Mechanobiology Institute, and.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Paris, France; and Centre d'Immunologie et de Maladies Infectieuses-Paris, INSERM, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore;
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore;
authors.forename: Bruce
authors.identifier: http://orcid.org/0000-0003-2333-4348
authors.initials: B
authors.lastname: Russell
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D004907:Erythrocyte Deformability; D006801:Humans; D016780:Malaria, Vivax / Q000097:blood / Q000469:parasitology; D010966:Plasmodium vivax / Q000254:growth & development*; D011990:Receptors, Transferrin / Q000378:metabolism*; D012156:Reticulocytes / Q000378:metabolism / Q000469:parasitology* / Q000502:physiology*; D018523:Tropism / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin