The Mechanism Of IL-10 In Improving Abnormal Pregnancy Following T.gondii Infection

Problem: To investigate the mechanism of IL-10 in reversing the abnormal pregnancy outcomes with T. gondii infection.Methods of study: The early pregnancy C57BL/6 wild type mice following T. gondii infection model was established to investigate the role of decidual regulatory T cells apptosis through extrinsic pathway in adverse pregnancy outcomes caused by T. gondii infection. Recombinant mouse IL-10 (rIL-10) treatment and IL-10 deficiency (IL-10.-/-)abnormal pregnancy animal model with T. gondii infection were established to explore the effect of IL-10 on regulating the apoptosis of decidual regulatory T cells through extrinsic pathway involved in improving the abnormal pregnancy outcomes following T. gondii infection. Four groups were divided in this study: the uninfected (WT) group,the infected group (IG), the infected mice with recombinant mouse IL-10 (rIL-10)treated group (rIL-10-treated group), and the infected IL-10-/- group (IL-10-/- group).The last three groups were infected with 400 T. gondii tachyzoite on gestational day(gd) 7. rIL-10 was injected via the tail vein at a dose of 1μg/mouse on gd 6 and gd 8 respectively in rIL-10-treated group. The mental statuses of mice in different groups were observed and all the mice were euthanized on gd 14. Pregnancy outcomes like the resorption rate, the necrotic and hemorrhagic appearance of embryos and placenta in each group were recorded. Placenta and uterus from each group were seperated to prepare single-cell suspensions. Apoptosis related molecules cleaved Caspase-3 and Caspase-8 in decidual regulatory T cells were examined using flow cytometry.Results: The mice exhibited more serious mental and behavioral disorders, such as flagging, shambling, extrados and moving less in the infected group than in uninfected WT group. More necrosis and resorbed fetuses phenotype were observed in the infected group compared to uninfected WT group. In addition, the resorption rate was significantly higher, and the mean weight of placenta and fetal were less in the infected group in contrast to the uninfected WT group. Compared with the infected group, the mental status and the pregnancy outcomes were better in rIL-10-treated group, and were worse in IL-10-/- group. Otherwise, the levels of cleaved Caspase-3 and Caspase-8 in decidual regulatory T cells were up-regulated with T. gondii infection. In contrast to the infected group, the expressions of cleaved Caspase-3 and Caspase-8 in decidual regulatory T cells were down-regulated in rIL-10-treated group, while up-regulated in the infected IL-10-/- group (IL-10-/-) group.Conclusion: T. gondii infection increased decidual regulatory T cells apoptosis through extrinsic pathway, leading to abnormal pregnancy outcomes. In addition,IL-10 reduced the decidual regulatory T cells apoptosis via extrinsic pathway contributed to improving adverse pregnant outcomes following T. gondii infection.This result maybe one of the mechanisms of IL-10 improving the adverse pregnancy caused by T. gondii infection.