Lucchi Naomi W, Peterson David S, Moore Julie M
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Malar J. 2008 Feb 29;7:42. doi: 10.1186/1475-2875-7-42.
Malaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bind to receptors expressed by the syncytiotrophoblast (ST). How ST responds to this interaction remains poorly understood. Because it is known that ST is immunoactive and can respond to infectious agents, the consequences of this ST-iRBC interaction should be investigated.
An in vitro system was used to assess the biochemical and immunological changes induced in ST by ST-adherent iRBCs. Changes in ST mitogen-activated protein kinase (MAPK) activation were assessed by immunoblotting and mRNA expression levels of selected cytokine and chemokines in primary ST bound by iRBC were determined using real-time, reverse transcription PCR. In addition, secreted cytokine and chemokine proteins were assayed by standard ELISA, and chemotaxis of PBMC was assessed using a two-chamber assay system.
Following iRBC/ST interaction, ST C-Jun N-terminal kinase 1 (JNK1) was activated and modest increases in the mRNA expression of TGF-beta and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1alpha/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST.
Results from this study provide the first evidence that ST participates in shaping the local immunological milieu and in the recruitment of maternal immune cells to the maternal blood space during placental malaria infection.
妊娠期疟疾的特征是疟原虫感染的红细胞（iRBC）滞留于胎盘绒毛间隙，常伴有母体单核细胞浸润，导致母体及胎儿/婴儿出现严重发病情况。iRBC与合体滋养层细胞（ST）表达的受体结合。目前对ST如何应对这种相互作用仍知之甚少。由于已知ST具有免疫活性且能对感染因子作出反应，因此应研究这种ST-iRBC相互作用的后果。
采用体外系统评估ST黏附的iRBC诱导ST发生的生化和免疫学变化。通过免疫印迹法评估ST丝裂原活化蛋白激酶（MAPK）激活的变化，并使用实时逆转录PCR测定iRBC结合的原代ST中选定细胞因子和趋化因子的mRNA表达水平。此外，通过标准ELISA检测分泌的细胞因子和趋化因子蛋白，并使用双室检测系统评估PBMC的趋化性。
iRBC/ST相互作用后，ST的C-Jun氨基末端激酶1（JNK1）被激活，观察到TGF-β和IL-8/CXCL8的mRNA表达略有增加。此外，这种相互作用增加了ST分泌MIF和MIP-1α/CCL3，并诱导PBMC向iRBC刺激的ST迁移。
本研究结果首次证明，在胎盘疟疾感染期间，ST参与塑造局部免疫环境并将母体免疫细胞募集到母体血腔。
