Antibody-dependent transplacental transfer of malaria blood-stage antigen using a human ex vivo placental perfusion model.
Antibody-dependent transplacental transfer of malaria blood-stage antigen using a human ex vivo placental perfusion model.
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DOI：
10.1371/journal.pone.0007986
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发表时间：
2009-11-24
期刊：
影响因子：
3.7
通讯作者：
King CL
中科院分区：
文献类型：
--
作者：
May K;Grube M;Malhotra I;Long CA;Singh S;Mandaliya K;Siegmund W;Fusch C;Schneider H;King CL
产前暴露于孕期感染释放的过敏原或抗原可刺激免疫反应或在胎儿中诱导免疫调节网络，影响日后感染和疾病的易感性。抗原是如何从母体环境进入胎儿环境的，目前还知之甚少。一种假说认为，经胎盘抗原转移是以免疫复合体的形式发生的，通过受体介导的跨合体滋养细胞膜和胎儿绒毛血管内皮细胞的转移。这一假设从未被直接检验过。在这里，我们研究了恶性疟原虫裂殖子表面蛋白1(MSP1)，它是在红细胞入侵时释放的。我们在三分之一感染疟疾的妇女的新生儿脐带血中发现了MSP1，在用酸解离治疗后90%的新生儿中发现了MSP1免疫复合体。使用体外人类胎盘模型，将胎盘子叶与独立的母体和胎儿回路双重灌流，免疫复合体MSP1从母体循环转移到胎儿循环。MSP1单独或与非免疫血浆不能转移；需要预先与含有抗MSP1的人血浆孵育。在胎儿灌流液中检测到与免疫球蛋白结合的MSP1。激光扫描共聚焦显微镜显示MSP1在胎儿绒毛间质中，主要在胎儿内皮细胞中。MSP1与Ig G共定位于内皮细胞，但不与胎盘巨噬细胞共定位。因此，我们第一次展示了抗体依赖的通过胎盘以免疫复合体的形式转移抗原。这些研究表明，胎儿经常接触某些抗原，这对妊娠期间母体感染的管理以及向胎儿提供疫苗或药物的新方法都有影响。
Prenatal exposure to allergens or antigens released by infections during pregnancy can stimulate an immune response or induce immunoregulatory networks in the fetus affecting susceptibility to infection and disease later in life. How antigen crosses from the maternal to fetal environment is poorly understood. One hypothesis is that transplacental antigen transfer occurs as immune complexes, via receptor-mediated transport across the syncytiotrophoblastic membrane and endothelium of vessels in fetal villi. This hypothesis has never been directly tested. Here we studied Plasmodium falciparum merozoite surface protein 1 (MSP1) that is released upon erythrocyte invasion. We found MSP1 in cord blood from a third of newborns of malaria-infected women and in >90% following treatment with acid dissociation demonstrating MSP1 immune complexes. Using an ex vivo human placental model that dually perfuses a placental cotyledon with independent maternal and fetal circuits, immune-complexed MSP1 transferred from maternal to fetal circulation. MSP1 alone or with non-immune plasma did not transfer; pre-incubation with human plasma containing anti-MSP1 was required. MSP1 bound to IgG was detected in the fetal perfusate. Laser scanning confocal microscopy demonstrated MSP1 in the fetal villous stroma, predominantly in fetal endothelial cells. MSP1 co-localized with IgG in endothelial cells, but not with placental macrophages. Thus we show, for the first time, antibody-dependent transplacental transfer of an antigen in the form of immune complexes. These studies imply frequent exposure of the fetus to certain antigens with implications for management of maternal infections during pregnancy and novel approaches to deliver vaccines or drugs to the fetus.
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