Rapid switching to multiple antigenic and adhesive phenotypes in malaria.
Rapid switching to multiple antigenic and adhesive phenotypes in malaria.
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DOI：
10.1038/357689a0
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发表时间：
1992-06-25
期刊：
影响因子：
64.8
通讯作者：
Newbold, C I
中科院分区：
文献类型：
--
作者：
Roberts, D J;Craig, A G;Berendt, A R;Pinches, R;Nash, G;Marsh, K;Newbold, C I
寄生红细胞对毛细血管后静脉内皮或未感染红细胞的粘附与严重恶性疟原虫疟疾的发病机制密切相关。受感染红细胞表面的新抗原粘附于多种宿主受体，在现场分离物中表现出血清学多样性，也可能是宿主保护性免疫反应的目标。在这里，我们通过显微操作连续克隆恶性疟原虫，以研究寄生虫转换抗原和细胞粘附表型的能力。我们的数据表明，在没有免疫压力的情况下，寄生细胞表面的抗原在体外以每代 2% 的速度发生克隆变异，并伴随着粘附表型的调节。克隆有可能以高频率转变为各种抗原和粘附表型，包括一种新型的细胞粘附行为，即受感染红细胞的“自动凝集”。这种抗原和功能异质性的快速出现对发病机制和获得性免疫具有重要意义。
Adhesion of parasitized erythrocytes to post-capillary venular endothelium or uninfected red cells is strongly implicated in the pathogenesis of severe Plasmodium falciparum malaria. Neoantigens at the infected red-cell surface adhere to a variety of host receptors, demonstrate serological diversity in field isolates and may also be a target of the host-protective immune response. Here we use sequential cloning of P. falciparum by micromanipulation to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, ‘auto-agglutination’ of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity.