Urban B C, Ferguson D J, Pain A, Willcox N, Plebanski M, Austyn J M, Roberts D J
Institute of Molecular Medicine, Oxford Centre, John Radcliffe Hospital, Headington, UK.
Nature. 1999 Jul 1;400(6739):73-7. doi: 10.1038/21900.
The malaria parasite Plasmodium falciparum is one of the most successful human pathogens. Specific virulence factors remain poorly defined, although the adhesion of infected erythrocytes to the venular endothelium has been associated with some of the syndromes of severe disease. Immune responses cannot prevent the development of symptomatic infections throughout life, and clinical immunity to the disease develops only slowly during childhood. An understanding of the obstacles to the development of protective immunity is crucial for developing rational approaches to prevent the disease. Here we show that intact malaria-infected erythrocytes adhere to dendritic cells, inhibit the maturation of dendritic cells and subsequently reduce their capacity to stimulate T cells. These data demonstrate both a novel mechanism by which malaria parasites induce immune dysregulation and a functional role beyond endothelial adhesion for the adhesive phenotypes expressed at the surface of infected erythrocytes.
疟原虫恶性疟原虫是最成功的人类病原体之一。尽管感染的红细胞与小静脉内皮细胞的黏附与一些严重疾病综合征有关,但具体的毒力因子仍未明确界定。免疫反应无法在一生中预防有症状感染的发生,并且对该疾病的临床免疫力在儿童期仅缓慢发展。了解保护性免疫发展的障碍对于制定合理的疾病预防方法至关重要。在此,我们表明完整的感染疟原虫的红细胞会黏附于树突状细胞,抑制树突状细胞的成熟,并随后降低其刺激T细胞的能力。这些数据既证明了疟原虫诱导免疫失调的新机制,也证明了感染红细胞表面表达的黏附表型在内皮黏附之外的功能作用。