Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes

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Malleret, Benoit | Li, Ang | Zhang, Rou | Tan, Kevin | Suwanarusk, Rossarin | Claser, Carla | Cho, Jee Sun | Koh, Esther Geok Liang | Chu, Cindy | Pukrittayakamee, Sasithon | Ng, Mah Lee | Ginhoux, Florent | Ng, Lai Guan | Lim, Chwee Teck | Nosten, François | Snounou, Georges | Rénia, Laurent | Russell, Bruce

Edité par CCSD ; American Society of Hematology -

International audience. 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.

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