Neutrophils impose strong selective pressure against PfEMP1 variants implicated in cerebral malaria
Neutrophils impose strong selective pressure against PfEMP1 variants implicated in cerebral malaria
复制标题
中性粒细胞对脑型疟疾中涉及的 PfEMP1 变异体施加强大的选择压力
DOI：
--
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Z. Granot
中科院分区：
文献类型：
--
作者：
Tamir Zelter;J. Strahilevitz;Karina Simantov;O. Yajuk;Anja M B Jensen;R. Dzikowski;Z. Granot
恶性疟原虫是人类疟疾中最致命的一种，在疟疾流行地区仍然是对人类健康的主要威胁之一。其毒力归因于其通过将称为PfEMP 1的可变抗原置于红细胞表面来修饰受感染的红细胞（iRBC）以粘附于内皮受体的能力。PfEMP 1在红细胞表面的表达决定了iRBC的细胞粘附特性，并与疟疾的严重表现有关。为了逃避抗体介导的反应，寄生虫在不同的PfEMP 1变体之间经历连续的表达转换。最近变得清楚的是，除了抗体介导的应答之外，PfEMP 1触发先天性免疫应答，然而，嗜中性粒细胞（人循环中最丰富的白色血细胞）在疟疾中的作用仍然难以捉摸。在这里，我们表明，中性粒细胞识别和杀死几个恶性疟原虫分离株的血液阶段，我们确定中性粒细胞ICAM-1和特定的PfEMP 1 s参与脑型疟疾的关键分子在这种杀伤。我们的数据为中性粒细胞和iRBC之间的相互作用提供了机制性的见解，并证明了PfEMP 1对脑型疟疾的选择性先天反应的重要影响。
Plasmodium falciparum, the deadliest form of human malaria, remains one of the major threats to human health in endemic regions. Its virulence is attributed to its ability to modify infected red blood cells (iRBC) to adhere to endothelial receptors by placing variable antigens known as PfEMP1 on the surface of the red cell. PfEMP1 expression on the red cell surface determines the cytoadhesive properties of the iRBCs and is implicated in severe manifestations of malaria. To evade antibody mediated responses the parasite undergoes continuous switches of expression between different PfEMP1 variants. Recently it became clear that in addition to antibody mediated responses, PfEMP1 triggers an innate immune response, however, the role of neutrophils, the most abundant white blood cells in the human circulation, in malaria remains elusive. Here we show that neutrophils recognize and kill blood stages of several P. falciparum isolates, and we identify neutrophil ICAM-1 and specific PfEMP1s implicated in cerebral malaria as the key molecules involved in this killing. Our data provide mechanistic insight into the interactions between neutrophils and iRBCs and demonstrate the important influence of PfEMP1 on the selective innate response to cerebral malaria.
影响因子：
14.9
作者：
Deitsch, KW;Driskill, CL;Wellems, TE
通讯作者：
Wellems, TE