Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C)
Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C)
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DOI：
10.1093/humrep/del178
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发表时间：
2006-09-01
影响因子：
6.1
通讯作者：
Mor, Gil
中科院分区：
文献类型：
--
作者：
Abrahams, Vikki M.;Schaefer, Todd M.;Mor, Gil
背景技术背景：在怀孕期间，胎盘可能会接触到微生物，如病毒，这可能会对胚胎/胎儿的健康构成重大威胁。最近对滋养层免疫能力的深入了解表明，胎盘可能通过Toll样受体（TLR）识别和响应病原体而发挥主动屏障的作用。方法：本研究的目的是确定TLR-3与病毒dsRNA通过妊娠早期滋养层的接合是否可以诱导产生产生抗病毒应答所需的因子。因此，将滋养层细胞暴露于TLR-3激动剂Poly（I：C）。研究结果：我们报告，在用Poly（I：C）刺激后，妊娠早期滋养层细胞产生干扰素β（IFN β）和分泌性白细胞蛋白酶抑制剂（SLPI），以及细胞内因子2 '，5'-寡腺苷酸合成酶（OAS）、粘病毒抗性A（MxA）和载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC 3G）。这种反应是TLR-3特异性的，因为TLR-4配体脂多糖（LPS）对这些抗菌因子的产生没有影响。此外，我们描述了一种正反馈机制，其中IFN β通过促进OAS、MxA和APOBEC 3G的产生来增强抗病毒反应。结论：这些研究结果表明，滋养层细胞能够识别和特异性反应的病毒产品在一个高度调节的方式和胎盘可能是关键的控制病毒感染的母胎界面。
BACKGROUND: During pregnancy, the placenta may become exposed to micro-organisms, such as viruses, which may pose a substantial threat to the embryo/fetus well-being. Recent insight into the immunological capabilities of the trophoblast suggests that the placenta may function as an active barrier by recognizing and responding to pathogens through Toll-like receptors (TLRs). METHODS: The objective of this study was to determine whether the engagement of TLR-3 with viral dsRNA by first-trimester trophoblast could induce the production of factors necessary to generate an antiviral response. Therefore, trophoblast cells were exposed to the TLR-3 agonist, Poly(I : C). RESULTS: We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon beta (IFN beta) and secretory leukocyte protease inhibitor (SLPI), as well as the intracellular factors 2',5'-oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). This response is TLR-3 specific because the TLR-4 ligand, lipopolysaccharide (LPS), had no effect on the production of these antimicrobial factors. Furthermore, we describe a positive feedback mechanism in which IFN beta enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G. CONCLUSIONS: These findings suggest that trophoblast cells are able to recognize and specifically respond to viral products in a highly regulated fashion and that the placenta may be pivotal in the control of viral infections at the maternal-fetal interface.