The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.

中文翻译：

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不同的表达 PfEMP1 的恶性疟原虫变体在共培养期间诱导不同的内皮转录反应。

人类疟疾寄生虫恶性疟原虫是造成疟疾感染引起的大部分死亡和发病的原因，并且与其他人类疟疾物种的不同之处在于被寄生虫感染的红细胞在微脉管系统中的积累程度，即细胞粘附或隔离。在恶性疟原虫中，细胞粘附是由一种名为 PfEMP1 的蛋白质介导的，该蛋白质由于暴露于宿主免疫系统而发生抗原变异，导致受感染的红细胞膜上表达不同的 PfEMP1 变体。这些 PfEMP1 包含不同的粘附结构域组合，允许宿主微血管系统上的内皮受体库进行差异性接合，并具有与严重疾病相关的特定受体使用。我们使用细胞粘附共培养模型，将人脑微血管内皮细胞与感染了表达不同 PfEMP1 的两种寄生虫系的红细胞一起孵育，这两种寄生虫系表现出与血管内皮的不同结合特征。我们确定了人脑微血管内皮细胞 (HBMEC) 在与受感染红细胞不同潜伏期后的转录谱，识别了先前发现与严重疟疾病理学有关的途径的不同转录谱，例如炎症、细胞凋亡和屏障完整性，诱导的由两个 PfEMP1 变体组成。