Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2011 Apr 12;6(4):e14798. doi: 10.1371/journal.pone.0014798.
In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.
We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.
Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.
在非洲，随着胎儿血红蛋白（HbF）和母体免疫 IgG 从循环中消失，婴儿对恶性疟原虫疟疾的易感性大大增加。然而，在生命的头几个月，对疟疾的抵抗力表现为极低的寄生虫血症、无发热和几乎完全没有严重疾病。这种抵抗力以前部分归因于含 HbF 的红细胞（RBC）中寄生虫的生长不良。母体免疫 IgG 在婴儿对疟疾的抵抗力中的具体作用已被假设但尚未确定。
我们发现恶性疟原虫寄生虫可以正常入侵和发育在胎儿（脐血，CB）RBC 中，这些 RBC 中含有高达 95%的 HbF。然而，这些被寄生虫感染的 CB RBC 在与人类微血管内皮细胞（MVEC）、单核细胞和未被寄生虫感染的 RBC 的结合方面受损，这些细胞粘附相互作用与寄生虫密度的升高和疟疾的症状有关。寄生虫的细胞粘附抗原恶性疟原虫红细胞膜蛋白-1（PfEMP-1）在 CB RBC 上的异常表达解释了这些发现，这让人想起在 HbC 和 HbS RBC 上的表达。从免疫的马里成年人的血浆中纯化的 IgG 几乎完全消除了寄生虫感染的 CB RBC 与 MVEC 的粘附。
我们的数据提出了一种疟疾保护模型，其中 HbF 和母体 IgG 协同作用，在生命的头几个月内削弱寄生虫感染 RBC 的细胞粘附。在非洲高度疟疾流行的地区，婴儿同时表达 HbC 或 HbS 并发展出免疫 IgG 库，可能会有效地重建 HbF 和母体免疫 IgG 逐渐消失的保护作用，从而将婴儿期的疟疾抵抗力延长到幼儿期。
