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

Blood (2014-11-22)
Benoit Malleret, Ang Li, Rou Zhang, Kevin S W Tan, Rossarin Suwanarusk, Carla Claser, Jee Sun Cho, Esther Geok Liang Koh, Cindy S Chu, Sasithon Pukrittayakamee, Mah Lee Ng, Florent Ginhoux, Lai Guan Ng, Chwee Teck Lim, François Nosten, Georges Snounou, Laurent Rénia, Bruce Russell
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
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Cellulose, fibers, (medium)
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Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
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Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
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Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
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Anti-Caveolin-1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)