Identification of Plasmodium falciparum-specific protein PIESP2 as a novel virulence factor related to cerebral malaria
Identification of Plasmodium falciparum-specific protein PIESP2 as a novel virulence factor related to cerebral malaria
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DOI：
10.1016/j.ijbiomac.2021.02.145
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发表时间：
2021-02-27
影响因子：
8.2
通讯作者：
Liang, Jiao
中科院分区：
文献类型：
--
作者：
Liu, Xuewu;Wu, Yongming;Liang, Jiao
脑型疟疾（CM）是恶性疟原虫感染引起的最严重的并发症。寄生虫毒力因子引起的病理生理变化和人体对寄生虫的免疫反应是导致CM的重要原因。迄今为止，很少有寄生虫毒力蛋白已被发现参与CM。在这里，我们采用比较基因组学分析，并确定寄生虫感染的红细胞特异性蛋白2（PIESP2）是CM相关蛋白。我们进行了进一步的实验研究，发现PIESP2是一种免疫原性蛋白。PIESP2表达开始于滋养体早期阶段，并随着寄生虫发育而逐渐增加。虽然PIESP2蛋白主要存在于受感染的红细胞（IRBC）内，但其中一些蛋白在色素阶段存在于IRBC表面。抗血清阻断PIESP 2可明显抑制IRBCs与脑微血管内皮细胞（BMEC）的粘附。Western blot分析检测PIESP2与BMEC的结合。转录分析显示，PIESP2与BMEC的结合可以增加参与炎症反应的基因的表达，但减少锚定连接相关基因的表达。PIESP 2可能通过介导IRBC的隔离、诱导炎症反应和损害血脑屏障的完整性而与CM相关。(c)2021由爱思唯尔公司出版
Cerebral malaria (CM) is the most severe complication caused by Plasmodium falciparum infection. The pathophysiological changes caused by parasite virulence factors and the human immune response to parasites contribute to CM. To date, very few parasite virulence proteins have been found to participate in CM. Here, we employed comparative genomics analysis and identified parasite-infected erythrocyte specific protein 2 (PIESP2) to be a CM-related protein. We conducted further experimental investigations and found that PIESP2 is an immunogenic protein. PIESP2 expression begins at the early trophozoite stage and progressively increases with parasite development. Although PIESP2 proteins mainly reside within infected red blood cells (IRBCs), some of them are present on the IRBC surface at the pigmented stage. Moreover, blockage of PIESP2 by antiserum apparently inhibited the adhesion of IRBCs to brain microvascular endothelial cells (BMECs). Western blot analysis detected the binding of PIESP2 to BMECs. Transcriptional analysis revealed that the binding of PIESP2 to BMECs can increase the expression of genes involved in the inflammatory response but decrease the expression of genes related to the anchoring junction. Overall, PIESP2 might be associated with CM by mediating the sequestration of IRBCs, inducing the inflammation response, and impairing the integrity of blood-brain barrier.(c) 2021 Published by Elsevier B.V.