Plasmodium vivax infection compromises reticulocyte stability.

Plasmodium vivax infection compromises reticulocyte stability.
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间日疟原虫感染损害网织红细胞稳定性。

DOI:
10.1038/s41467-021-21886-x
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发表时间:
2021-03-12
影响因子:
16.6
通讯作者:
Duraisingh MT
Duraisingh MT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Clark MA;Kanjee U;Rangel GW;Chery L;Mascarenhas A;Gomes E;Rathod PK;Brugnara C;Ferreira MU;Duraisingh MT

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宿主红细胞(RBC)的结构完整性对于疟原虫的繁殖至关重要。在疟疾感染的致病血液阶段。为了评估间日疟原虫感染的网织红细胞的稳定性,我们开发了一种基于流式细胞术的测定方法,以测量特征性异质网织红细胞和间日疟原虫感染的样品中的渗透稳定性。我们发现,红系渗透稳定性下降,在红细胞生成和网织红细胞成熟。在去核红细胞中,优先被间日疟原虫感染的年轻网织红细胞是最稳定的。然而,间日疟原虫感染使网织红细胞稳定性降低至接近导致溶血性贫血的红细胞疾病的水平,并且比恶性疟原虫使正常细胞不稳定的程度显着更大。最后,我们发现间日疟原虫新的渗透途径有助于降低感染网织红细胞的渗透稳定性。这些结果揭示了间日疟原虫感染的网织红细胞的脆弱性,可以对其进行操纵以允许体外培养和开发新的治疗方法。在疟原虫红细胞内发育期间,寄生虫损害宿主红细胞的结构完整性。在此,Clark等人开发了流式细胞术渗透稳定性测定,以显示间日疟原虫感染使宿主网织红细胞不稳定,其不如恶性疟原虫感染的正常细胞稳定。
The structural integrity of the host red blood cell (RBC) is crucial for propagation of Plasmodium spp. during the disease-causing blood stage of malaria infection. To assess the stability of Plasmodium vivax-infected reticulocytes, we developed a flow cytometry-based assay to measure osmotic stability within characteristically heterogeneous reticulocyte and P. vivax-infected samples. We find that erythroid osmotic stability decreases during erythropoiesis and reticulocyte maturation. Of enucleated RBCs, young reticulocytes which are preferentially infected by P. vivax, are the most osmotically stable. P. vivax infection however decreases reticulocyte stability to levels close to those of RBC disorders that cause hemolytic anemia, and to a significantly greater degree than P. falciparum destabilizes normocytes. Finally, we find that P. vivax new permeability pathways contribute to the decreased osmotic stability of infected-reticulocytes. These results reveal a vulnerability of P. vivax-infected reticulocytes that could be manipulated to allow in vitro culture and develop novel therapeutics. During Plasmodium intra-erythrocytic developmental, parasites compromise the structural integrity of host red-blood cells. Here, Clark et al. develop a flow cytometric osmotic stability assay to show that P. vivax infection destabilizes host reticulocytes, which are less stable than P. falciparum-infected normocytes.
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