Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
PLoS One. 2009 Oct 14;4(10):e7459. doi: 10.1371/journal.pone.0007459.
To avoid spleen-dependent killing mechanisms parasite-infected erythrocytes (IE) of Plasmodium falciparum malaria patients have the capacity to bind to endothelial receptors. This binding also known as sequestration, is mediated by parasite proteins, which are targeted to the erythrocyte surface. Candidate proteins are those encoded by P. falciparum multicopy gene families, such as var, rif, stevor or PfMC-2TM. However, a direct in vivo proof of IE sequestration and expression of multicopy gene families is still lacking. Here, we report on the analysis of IE from a black African immigrant, who received the diagnosis of a malignant lymphoproliferative disorder and subsequently underwent splenectomy. Three weeks after surgery, the patient experienced clinical falciparum malaria with high parasitemia and circulating developmental parasite stages usually sequestered to the vascular endothelium such as late trophozoites, schizonts or immature gametocytes.
METHODOLOGY/PRINCIPAL FINDINGS: Initially, when isolated from the patient, the infected erythrocytes were incapable to bind to various endothelial receptors in vitro. Moreover, the parasites failed to express the multicopy gene families var, A-type rif and stevor but expression of B-type rif and PfMC-2TM genes were detected. In the course of in vitro cultivation, the parasites started to express all investigated multicopy gene families and concomitantly developed the ability to adhere to endothelial receptors such as CD36 and ICAM-1, respectively.
CONCLUSION/SIGNIFICANCE: This case strongly supports the hypothesis that parasite surface proteins such as PfEMP1, A-type RIFIN or STEVOR are involved in interactions of infected erythrocytes with endothelial receptors mediating sequestration of mature asexual and immature sexual stages of P. falciparum. In contrast, multicopy gene families coding for B-type RIFIN and PfMC-2TM proteins may not be involved in sequestration, as these genes were transcribed in infected but not sequestered erythrocytes.
为了避免依赖脾脏的杀伤机制，恶性疟原虫感染的红细胞（IE）具有与内皮受体结合的能力。这种结合也称为附壁，是由寄生虫蛋白介导的，这些蛋白被靶向到红细胞表面。候选蛋白是那些由恶性疟原虫多拷贝基因家族编码的蛋白，如 var、rif、stevor 或 PfMC-2TM。然而，IE 附壁和多拷贝基因家族表达的直接体内证据仍然缺乏。在这里，我们报告了一位非洲裔移民患者的 IE 分析，该患者被诊断为恶性淋巴增生性疾病，随后接受了脾切除术。手术后 3 周，患者出现了恶性疟原虫引起的临床疟疾，伴有高寄生虫血症和循环发育中的寄生虫阶段，这些阶段通常会附壁到血管内皮，如晚期滋养体、裂殖体或未成熟配子体。
方法/主要发现：最初，从患者中分离出来的感染红细胞在体外不能与各种内皮受体结合。此外，寄生虫未能表达多拷贝基因家族 var、A 型 rif 和 stevor，但检测到 B 型 rif 和 PfMC-2TM 基因的表达。在体外培养过程中，寄生虫开始表达所有研究的多拷贝基因家族，并同时发展出与内皮受体如 CD36 和 ICAM-1 结合的能力。
结论/意义：这个病例强烈支持了这样一种假设，即寄生虫表面蛋白如 PfEMP1、A 型 RIFIN 或 STEVOR 参与了感染红细胞与内皮受体的相互作用，介导了恶性疟原虫成熟无性和未成熟有性阶段的附壁。相比之下，编码 B 型 RIFIN 和 PfMC-2TM 蛋白的多拷贝基因家族可能不参与附壁，因为这些基因在感染但未附壁的红细胞中转录。
