Chen Q, Schlichtherle M, Wahlgren M
Microbiology and Tumour Biology Centre, Karolinska Institutet, and Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.
Clin Microbiol Rev. 2000 Jul;13(3):439-50. doi: 10.1128/CMR.13.3.439.
Human infections with Plasmodium falciparum may result in severe forms of malaria. The widespread and rapid development of drug resistance in P. falciparum and the resistance of the disease-transmitting mosquitoes to insecticides make it urgent to understand the molecular background of the pathogenesis of malaria to enable the development of novel approaches to combat the disease. This review focuses on the molecular mechanisms of severe malaria caused by the P. falciparum parasite. The nature of severe malaria and the deleterious effects of parasite-derived toxins and host-induced cytokines are introduced. Sequestration, brought about by cytoadherence and rosetting, is linked to severe malaria and is mediated by multiple receptors on the endothelium and red blood cells. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority of binding interactions, and the multiply adhesive features of this sticky molecule are presented. Antigenic variation is also a major feature of PfEMP1 and of the surface of the P. falciparum-infected erythrocyte. Possible mechanisms of P. falciparum antigenic variation in asexual stages are further discussed. We conclude this review with a perspective and suggestions of important aspects for future investigations.
人类感染恶性疟原虫可能会导致严重形式的疟疾。恶性疟原虫耐药性的广泛快速发展以及传播疾病的蚊子对杀虫剂的抗性，使得了解疟疾发病机制的分子背景以开发对抗该疾病的新方法变得紧迫。本综述聚焦于由恶性疟原虫引起的严重疟疾的分子机制。介绍了严重疟疾的本质以及寄生虫衍生毒素和宿主诱导细胞因子的有害影响。由细胞粘附和红细胞凝聚引起的滞留与严重疟疾相关，并且由内皮细胞和红细胞上的多种受体介导。恶性疟原虫红细胞膜蛋白1（PfEMP1）是负责大多数结合相互作用的配体，并介绍了这种粘性分子的多重粘附特性。抗原变异也是PfEMP1以及恶性疟原虫感染红细胞表面的一个主要特征。进一步讨论了恶性疟原虫无性阶段抗原变异的可能机制。我们以对未来研究重要方面的展望和建议结束本综述。
