Glycosylphosphatidylinositol anchors of Plasmodium falciparum:: Molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis
Glycosylphosphatidylinositol anchors of Plasmodium falciparum:: Molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis
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DOI：
10.1084/jem.192.11.1563
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发表时间：
2000-12-04
影响因子：
15.3
通讯作者：
Gowda, DC
中科院分区：
文献类型：
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作者：
Naik, RS;Branch, OH;Gowda, DC
红细胞内恶性疟原虫的糖基磷脂酰肌醇（GPIs）诱导的促炎细胞因子反应被认为有助于疟疾的发病机制。本研究对恶性疟原虫GPIs进行了纯化，并通过生化降解和质谱分析确定了其结构。寄生虫GPIs与宿主GPIs的不同之处在于，它们在肌醇的C-2处含有棕榈酸（主要）和肉豆蔻酸（次要），主要是分别在sn-1和sn-2处的C18：0和C18：1，并且在其核心聚糖结构中不含额外的磷酸乙醇胺取代。纯化的寄生虫GPIs可诱导巨噬细胞释放肿瘤坏死因子α。我们还报告了一项新的发现，即对临床疟疾具有抵抗力的成年人含有高水平的持久性抗GPI抗体，而易感儿童缺乏或具有低水平的短期抗体应答。没有接触疟疾寄生虫的人完全缺乏抗GPI抗体。持续性抗GPI抗体应答的缺乏与疟疾特异性贫血和发热相关，表明抗GPI抗体提供了针对临床疟疾的保护。抗体主要针对GPIs的酰化磷酸肌醇部分。这些结果可能在旨在评价化学定义结构的毒性与免疫原性的研究中具有价值，并对基于GPI的治疗或疫苗的开发产生影响。
Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to contribute to malaria pathogenesis. In this study, we purified the GPIs of P. falciparum to homogeneity and determined their structures by biochemical degradations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C-2 of inositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectively, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosis factor a release from macrophages. We also report a new finding that adults who have resistance to clinical malaria contain high levels of persistent anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persistent anti-GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria. The antibodies are mainly directed against the acylated phosphoinositol portion of GPIs. These results are likely to be valuable in studies aimed at the evaluation of chemically defined structures for toxicity versus immunogenicity with implications for the development of GPI-based therapies or vaccines.