Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression.

Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression.
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DOI:
10.1128/mbio.03391-22
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发表时间:
2023-04-25
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学1区
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脑型疟疾(CM)是疟原虫感染最致命的并发症,是一种复杂且不可预测的疾病。然而,我们对引起 CM 的宿主和寄生虫因素的了解有限。使用 CM 小鼠模型,实验 CM (ECM),我们对感染引起 ECM 的疟原虫 ANKA 寄生虫 [ANKA(C57BL/6)] 的 ECM 敏感 C57BL/6 小鼠、感染疟原虫 ANKA 的 ECM 抗性 BALB/c 小鼠 [ANKA(BALB/c)] 和感染疟原虫 NK65 的 C57BL/6 小鼠进行三向比较。不会引起 ECM [NK65(C57BL/6)]。所有 ANKA(C57BL/6) 小鼠均出现 CM。相比之下,在 ANKA(BALB/c) 和 NK65(C57BL/6) 中,感染不会导致 CM,并且在寄生虫生长、病程和宿主免疫反应方面的进展相似。然而,ANKA(BALB/c)中的寄生虫基因表达与ANKA(C57BL/6)中的显着不同,但与NK65(C57BL/6)中的基因表达相似。因此,疟原虫 ANKA 具有 ECM 特异性基因表达谱,仅在易感宿主中激活,这提供了宿主对感染结果具有关键影响的证据。
Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection.
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