Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains
Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains
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DOI：
10.4049/jimmunol.0901331
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发表时间：
2009-09-01
影响因子：
4.4
通讯作者：
Theander, Thor G.
中科院分区：
文献类型：
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作者：
Cham, Gerald K. K.;Turner, Louise;Theander, Thor G.
被成熟的血液期寄生虫感染的红细胞与血管床的结合是恶性疟疾发病机制的关键。这种结合是由恶性疟原虫红细胞膜蛋白1（PfEMP 1）家族成员介导的。PfEMP 1可以分为几组，以前曾提出，表达A组或B/A PfEMP 1的寄生虫是最致病的。为了检验婴儿和幼儿的首次疟疾感染主要由表达A和B/A PfEMP 1的寄生虫主导的假设，我们测量了生活在5个非洲村庄的1342名个体的血浆抗体水平，这些个体的疟疾传播特征明显不同。我们发现，儿童逐渐获得更广泛的抗PfEMP 1抗体库，但扩张的速度是由传输强度。然而，与透射强度无关，Ab首先获得属于A组或B/A PfEMP 1的特定达菲结合配体样结构域。结果支持这样的观点，即抗PfEMP 1抗体反应有效地构建了由寄生虫维持的PfEMP 1库的支出。表达某些A组和B/A PfEMP 1的寄生虫首先由先前暴露有限的个体响应，并且所产生的抗体在随后的感染期间降低这些寄生虫的适应性和致病性。这使得表达致病性较低的PFEMP 1的寄生虫在以后的感染中占主导地位。鉴定引起婴儿和幼儿疾病的寄生虫表达的PfEMP 1结构域对于开发预防严重疟疾的疫苗非常重要。免疫学杂志，2009，183：3356-3363.
The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key to the pathogenesis of malignant malaria. The binding is mediated by members of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has previously been suggested that parasites expressing group A or B/A PfEMP1s are most pathogenic. To test the hypothesis that the first malaria infections in infants and young children are dominated by parasites expressing A and B/A PfEMP1s, we measured the plasma Ab level against 48 recombinant PfEMP1 domains of different groupings in 1342 individuals living in five African villages characterized by markedly different malaria transmission. We show that children progressively acquire a broader repertoire of anti-PfEMP1 Abs, but that the rate of expansion is governed by transmission intensity. However, independently of transmission intensity, Abs are first acquired to particular duffy binding ligand-like domains belonging to group A or B/A PfEMP1s. The results support the view that anti-PfEMP1 Ab responses effectively structure the expenditure of the repertoire of PfEMP1 maintained by the parasite. Parasites expressing certain group A and B/A PfEMP1s are responded to first by individuals with limited previous exposure, and the resulting Abs reduce the fitness and pathogenicity of these parasites during subsequent infections. This allows parasites expressing less pathogenic PFEMP1s to dominate during later infections. The identification of PfEMP1 domains expressed by parasites causing disease in infants and young children is important for development of vaccines protecting against severe malaria. The Journal of Immunology, 2009, 183: 3356-3363.