Data_Sheet_1_Cytoadherence Properties of Plasmodium knowlesi-Infected Erythrocytes.docx

Plasmodium knowlesi is responsible for zoonotic malaria infections that are potentially fatal. While the severe pathology of falciparum malaria is associated with cytoadherence phenomena by Plasmodium falciparum-infected erythrocytes (IRBC), information regarding cytoadherence properties of P. knowlesi-IRBC remained scarce. Here, we characterized the cytoadherence properties of RBC infected with the laboratory-adapted P. knowlesi A1-H.1 strain. We found that late-stage IRBC formed rosettes in a human serum-dependent manner, and rosettes hampered IRBC phagocytosis. IRBC did not adhere much to unexposed (unstimulated) human endothelial cell lines derived from the brain (hCMEC/D3), lungs (HPMEC), and kidneys (HRGEC). However, after being “primed” with P. knowlesi culture supernatant, the IRBC-endothelial cytoadherence rate increased in HPMEC and HRGEC, but not in hCMEC/D3 cells. Both endothelial cytoadherence and rosetting phenomena were abrogated by treatment of P. knowlesi-IRBC with trypsin. We also found that different receptors were involved in IRBC cytoadherence to different types of endothelial cells. Although some of the host receptors were shared by both P. falciparum- and P. knowlesi-IRBC, the availability of glycoconjugates on the receptors might influence the capacity of P. knowlesi-IRBC to cytoadhere to these receptors.

诺氏疟原虫（Plasmodium knowlesi）可引发具有潜在致死性的人畜共患疟疾感染。恶性疟原虫（Plasmodium falciparum）感染的红细胞（受染红细胞，infected erythrocytes, IRBC）所介导的细胞黏附现象，与其引发的恶性疟疾严重病理特征密切相关；而目前关于诺氏疟原虫感染的受染红细胞（P. knowlesi-IRBC）的细胞黏附特性的相关研究资料仍较为匮乏。本研究针对实验室适应株诺氏疟原虫A1-H.1感染的红细胞的细胞黏附特性进行了系统表征。研究发现，晚期阶段的受染红细胞以人血清依赖性方式形成玫瑰花结，且该玫瑰花结结构会阻碍受染红细胞的吞噬作用。受染红细胞与未经过刺激的人脑源内皮细胞系hCMEC/D3、肺源内皮细胞系HPMEC以及肾源内皮细胞系HRGEC的黏附能力较弱。但经诺氏疟原虫培养上清预刺激后，受染红细胞与HPMEC和HRGEC的细胞黏附率显著升高，而该效应在hCMEC/D3细胞中未观察到。使用胰蛋白酶处理诺氏疟原虫感染的受染红细胞后，其内皮细胞黏附与玫瑰花结形成两种现象均被完全阻断。本研究还发现，受染红细胞对不同类型内皮细胞的黏附过程涉及不同的宿主受体。尽管部分宿主受体同时被恶性疟原虫和诺氏疟原虫感染的受染红细胞所共用，但受体表面糖结合物的可及性可能会影响诺氏疟原虫感染的受染红细胞对这些受体的黏附能力。