RAPID SWITCHING TO MULTIPLE ANTIGENIC AND ADHESIVE PHENOTYPES IN MALARIA

被引:528
作者
ROBERTS, DJ [1 ]
CRAIG, AG [1 ]
BERENDT, AR [1 ]
PINCHES, R [1 ]
NASH, G [1 ]
MARSH, K [1 ]
NEWBOLD, CI [1 ]
机构
[1] UNIV BIRMINGHAM,DEPT HAEMATOL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1038/357689a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
ADHESION of parasitized erythrocytes to post-capillary venular endothelium 1 or uninfected red cells 2-4 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 5-9, demonstrate serological diversity in field isolates 10,11 and may also be a target of the host-protective immune response 12. 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.
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页码:689 / 692
页数:4
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