Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes
Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes
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DOI：
10.1182/blood-2014-08-596015
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发表时间：
2015-02-19
期刊：
影响因子：
20.3
通讯作者：
Russell, Bruce
中科院分区：
文献类型：
--
作者：
Malleret, Benoit;Li, Ang;Russell, Bruce
间日疟原虫的分裂子仅侵袭网织红细胞，网织红细胞是红细胞前体的一种微小但异质性的群体，可以通过转铁蛋白受体（CD71）的表达水平来分级。一种允许将网织红细胞分选到确定的发育阶段的方案的发展和一种强大的离体间日疟原虫入侵试验，首次使研究间日疟原虫分裂子的精细入侵偏好成为可能。令人惊讶的是，通常局限于骨髓的未成熟网状细胞（CD71(+)）优先被侵入，而主要存在于外周血中的老年网状细胞（CD71(-)）很少被侵入。基于CD71（+）网织细胞分数的侵袭试验显示了大量的侵袭后修饰。因此，侵袭后3至6小时，最初生物力学上坚硬的CD71（+）网状红细胞转化为高度变形的CD71（-）感染红细胞，缺乏宿主网状物质，这一过程对于未感染的网状红细胞通常持续24小时。与这些变化同时发生的是，网格蛋白凹坑在入侵后3小时消失，取而代之的是独特的微泡纳米结构。间日疟原虫侵袭的两个迄今未被怀疑的特征，对未成熟网状细胞的狭窄偏好和宿主细胞的快速重塑，为间日疟原虫感染的病理生物学提供了重要的见解。
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.