Université de Paris, MERIT, IRD, Paris, France.
Centre for Medical Parasitology at Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Infect Dis. 2020 Jun 11;221(12):2010-2017. doi: 10.1093/infdis/jiaa043.
Plasmodium falciparum-infected erythrocytes bind to specific endothelial cell receptors via members of the PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich interdomain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRα1 domains bind endothelial protein C receptor (EPCR), CIDRα2-6 domains bind CD36, whereas the receptor specificity of CIDRβ/γ/δ domains is unknown.
In this study, we investigated the level of immunoglobulin (Ig)G targeting the different types of PfEMP1 CIDR during the first year of life. We used plasma collected longitudinally from children of pregnant women who had been followed closely through pregnancy.
Antibodies to CIDRα1 domains were more frequent in cord blood compared with antibodies to CIDRα2-6 domains. Higher IgG levels to EPCR-binding CIDRα1 variants positively correlated with the timing of first infections. Antibodies to all PfEMP1 types declined at similar rates to the point of disappearance over the first 6 months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P falciparum infections.
These observations agree with the notion that the timing and phenotype of first P falciparum infections in life are influenced by the immune status of the mother.
疟原虫感染的红细胞通过表面表达的 PfEMP1 家族成员与特定的内皮细胞受体结合。这些相互作用是由 PfEMP1 N 端区域中不同类型的富含半胱氨酸的结构域间区(CIDR)介导的。CIDRα1 结构域结合内皮蛋白 C 受体(EPCR),CIDRα2-6 结构域结合 CD36,而 CIDRβ/γ/δ 结构域的受体特异性尚不清楚。
在这项研究中,我们研究了在生命的第一年中针对不同类型 PfEMP1 CIDR 的免疫球蛋白(IgG)水平。我们使用从孕妇的纵向采集的血浆进行研究,这些孕妇在怀孕期间得到了密切的随访。
与 CIDRα2-6 结构域相比,脐血中针对 CIDRα1 结构域的抗体更为常见。与 EPCR 结合的 CIDRα1 变体的 IgG 水平越高,首次感染的时间就越早。针对所有 PfEMP1 类型的抗体以相似的速度下降,在生命的前 6 个月内消失。在 12 个月时,儿童获得了针对所有 CIDR 结构域类型的抗体,这主要发生在有记录的恶性疟原虫感染的儿童中。
这些观察结果与以下观点一致,即生命中首次恶性疟原虫感染的时间和表型受母亲免疫状态的影响。