SICA-mediated cytoadhesion of Plasmodium knowlesi-infected red blood cells to human umbilical vein endothelial cells.

SICA-mediated cytoadhesion of Plasmodium knowlesi-infected red blood cells to human umbilical vein endothelial cells.
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DOI:
10.1038/s41598-022-19199-0
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发表时间:
2022-09-02
期刊:
影响因子:
4.6
通讯作者:
Kaneko, Osamu
Kaneko, Osamu
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chuang, Huai;Sakaguchi, Miako;Lucky, Amuza Byaruhanga;Yamagishi, Junya;Katakai, Yuko;Kawai, Satoru;Kaneko, Osamu

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在东南亚,由诺氏疟原虫感染引起的人畜共患疟疾有时会危及生命。对人类诺氏疟疾病例的尸检显示,诺氏疟原虫感染的红细胞(iRBC)在血管中被隔离,这被认为与疾病的严重程度有关。这种隔离可能是由寄生虫-iRBC与血管内皮细胞的细胞粘附介导的;然而,负责的寄生虫配体仍然未确定。本研究通过对人脐静脉内皮细胞(HUVEC)重复淘选,选择了iRBC细胞粘附活性增加的诺氏毕赤酵母细胞系。转录组分析显示,编码裂殖体感染细胞凝集(SICA)蛋白的一个基因(本文称为SICA-HUVEC)的转录水平在淘选后增加超过100倍。其他诺氏毕赤酵母蛋白的转录物也显著增加,例如输出到iRBC胞质溶胶的PIR蛋白,表明它们在增加细胞粘附活性中的潜在作用。表达Myc融合SICA-HUVEC的转基因诺氏疟原虫在感染猴以及人RBC后增加了细胞粘附活性,证实SICA-HUVEC传递与HUVEC结合的活性。
Zoonotic malaria due to Plasmodium knowlesi infection in Southeast Asia is sometimes life-threatening. Post-mortem examination of human knowlesi malaria cases showed sequestration of P. knowlesi-infected red blood cells (iRBCs) in blood vessels, which has been proposed to be linked to disease severity. This sequestration is likely mediated by the cytoadhesion of parasite-iRBCs to vascular endothelial cells; however, the responsible parasite ligands remain undetermined. This study selected P. knowlesi lines with increased iRBC cytoadhesion activity by repeated panning against human umbilical vein endothelial cells (HUVECs). Transcriptome analysis revealed that the transcript level of one gene, encoding a Schizont Infected Cell Agglutination (SICA) protein, herein termed SICA-HUVEC, was more than 100-fold increased after the panning. Transcripts of other P. knowlesi proteins were also significantly increased, such as PIR proteins exported to the iRBC cytosol, suggesting their potential role in increasing cytoadhesion activity. Transgenic P. knowlesi parasites expressing Myc-fused SICA-HUVEC increased cytoadhesion activity following infection of monkey as well as human RBCs, confirming that SICA-HUVEC conveys activity to bind to HUVECs.
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