TLR3参与poly(I-C)所致流产的作用

Role of toll-like receptor 3 in poly(I-C)-induced abortion

目的研究Toll样受体3(toll-like receptor 3,TLR3)在poly(I-C)诱发小鼠流产中的潜在作用。方法多聚次黄苷酸-胞苷酸[polyinosinic-polycytidync acid,poly(I-C)]是一种双链RNA,腹腔注射时能够诱发小鼠流产。在预先用单抗阻断或不阻断TLR3情况下,注射poly(I-C)建立小鼠诱发性流产模型,应用流式细胞术分别检测CD45+DX5+和DX5+CD69+细胞百分率。结果不用抗TLR3抗体预处理,单用poly(I-C)刺激同种异基因交配模型BALB/c×C57BL/6,可使CD45+DX5+和DX5+CD69+细胞百分率均显著升高。但是,应用抗TLR3抗体预处理的雌鼠,用poly(I-C)刺激时上述百分率不改变。与此相应,poly(I—C)刺激可显著增高胚胎吸收率,而抗TLR3抗体预处理可消除这种作用。结论poly(I-C)与TLR3结合可能对母-胎界面NK细胞活化至关重要,并可促进小鼠胚胎吸收。

Objective To investigate the potential role of Toll-like receptor 3（TLR3） in the mechanism of poly（I-C）-induced abortion. Methods The administration of poly（I-C） （polyinosinic-polycytidylic acid） was performed to establish a murine model of induced embryo-resorption, with or without TLR3-blocking by multiple-injections of McAb against TLR3. Flow cytometric analysis was carried out to detect the percentage of CD45 ^＋ DX5 ^＋ and DX5 ^＋ CD69 ^＋ cell subsets. Results In the allogeneic mating model, BALB/c × C57BL/6, both the CD45 ^＋ DX5^＋ and DX5^＋ CD69^＋ cell percentages were significantly elevated upon poly（I-C） stimulation in the absence of anti-TLR3 administration, but kept unchanged if the female mice were pretreated with anti-TLR3 McAb. Accordingly, the resorption rate of embryos was boosted by poly（I-C）-administration, but this effect could be abrogated by pretreatment of anti-TLR3 McAb. Conclusion The engagement of poly（I-C） with TLR3 may be critical to the activation of NK cells infiltrated at the feto-maternal interface, resulting in the elevated embryo-resorption.