Abrahams Vikki M, Schaefer Todd M, Fahey John V, Visintin Irene, Wright Jacqueline A, Aldo Paulomi B, Romero Roberto, Wira Charles R, Mor Gil
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Hum Reprod. 2006 Sep;21(9):2432-9. doi: 10.1093/humrep/del178. Epub 2006 Jun 3.
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).
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).
We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon beta (IFNbeta) 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 IFNbeta enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G.
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.
在孕期，胎盘可能会接触到微生物，如病毒，这可能对胚胎/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）识别并应对病原体，从而发挥主动屏障的作用。
本研究的目的是确定孕早期滋养层细胞通过TLR-3与病毒双链RNA结合是否能诱导产生抗病毒反应所需的因子。因此，将滋养层细胞暴露于TLR-3激动剂聚肌苷酸-聚胞苷酸（Poly(I:C)）。
我们报告，在用Poly(I:C)刺激后，孕早期滋养层细胞产生干扰素β（IFNβ）、分泌型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）、抗腮腺炎病毒A（MxA）和载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G）。这种反应具有TLR-3特异性，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IFNβ通过促进OAS、MxA和APOBEC3G的产生来增强抗病毒反应。
这些发现表明，滋养层细胞能够以高度调控的方式识别并特异性地应对病毒产物，并且胎盘在母胎界面的病毒感染控制中可能起着关键作用。
