Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient.
Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient.
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DOI：
10.1371/journal.pone.0007459
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发表时间：
2009-10-14
期刊：
影响因子：
3.7
通讯作者：
Tannich E
中科院分区：
文献类型：
--
作者：
Bachmann A;Esser C;Petter M;Predehl S;von Kalckreuth V;Schmiedel S;Bruchhaus I;Tannich E
为了避免脾依赖的杀伤机制，恶性疟疾患者的寄生虫感染的红细胞(IE)具有与内皮受体结合的能力。这种结合也称为隔离，是由针对红细胞表面的寄生虫蛋白介导的。候选蛋白是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，多拷贝基因家族的IE隔离和表达的直接体内证据仍然缺乏。在这里，我们报告了一名非洲黑人移民的IE分析，他被诊断为恶性淋巴增生性疾病，随后接受了脾切除术。术后3周，患者出现高原虫血症的临床恶性疟疾，循环发育的寄生虫期通常隔离在血管内皮细胞，如晚期滋养体、裂殖体或未成熟的配子体。最初，当从患者身上分离时，感染的红细胞在体外无法与各种内皮受体结合。此外，寄生虫不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，并分别与CD36和ICAM-1等内皮受体结合。该病例有力地支持了PfEMP1、A型RIFIN或STEVOR等寄生虫表面蛋白参与感染红细胞与内皮受体相互作用的假说，内皮受体介导了恶性疟原虫成熟的无性和未成熟性阶段的隔离。相反，编码B型RIFIN和PfMC-2TM蛋白的多拷贝基因家族可能不参与隔离，因为这些基因在感染的红细胞中转录，而不是隔离的红细胞中转录。
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. 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. 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.
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