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弓形虫感染孕鼠中 Treg/Th17 失衡。

The Treg/Th17 imbalance in Toxoplasma gondii-infected pregnant mice.

机构信息

Department of Immunology, Binzhou Medical College, Yantai, China.

出版信息

Am J Reprod Immunol. 2012 Feb;67(2):112-21. doi: 10.1111/j.1600-0897.2011.01065.x. Epub 2011 Sep 19.

Abstract

AIM

To evaluate whether impaired Treg/Th17 balance exists in the pregnant mice infected with Toxoplasma gondii.

METHOD OF STUDY

Regulatory T (Treg) and T-helper type 17 (Th17) cells were measured in both placenta and spleens of the pregnant mice infected with and without T. gondii by flow cytometry. The mRNA and protein expression levels of transforming growth factor-β (TGF-β) and interleukin-17A (IL-17A) were analyzed using real-time PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of forkhead box P3 (Foxp3), retinoic acid-related orphan receptor γt (RORγt), and IL-6 were also analyzed using real-time PCR. The correlations of the ratio of Treg/Th17 to the mRNA or protein expression level of those factors were analyzed by Spearman's correlation analysis. Data were analyzed by unpaired t-test and paired t-test.

RESULTS

The proportion of Tregs or Th17 cells in the placenta and spleens of the T. gondii-infected pregnant mice was significantly lower or higher than in those of non-infected mice, respectively. Upregulation of TGF-β and downregulation of IL-17A were found in the placenta of T. gondii-infected pregnant mice. The ratio of Treg to Th17 was significantly lower in the infected mice than that in the non-infected mice (P<0.01).The ratio of Treg to Th17 positively or negatively correlated with the protein expression level of TGF-β (r=0.6204, P<0.05) or IL-17A (r=-0.6296, P<0.05), respectively. The ratio also positively correlated with the mRNA expression level of Foxp3 (r=0.7985, P<0.01), but negatively correlated with the mRNA expression level of RORγt (r=-0.6153, P<0.05), and IL-6 (r=-0.7492, P<0.01).

CONCLUSION

TheTreg/Th17 imbalance exists in the pregnant mice infected with T. gondii, which is associated with the expression of related cytokine and key transcription factors. This result suggests that the embryo loss caused by this parasite may be associated with a reduced ratio of Treg to Th17 cell number.

摘要

目的

评估感染弓形虫的妊娠小鼠是否存在调节性 T(Treg)/辅助性 T 细胞 17(Th17)失衡。

研究方法

通过流式细胞术检测感染和未感染弓形虫的妊娠小鼠胎盘和脾脏中的调节性 T 细胞(Treg)和辅助性 T 细胞 17(Th17)细胞。实时 PCR 和酶联免疫吸附试验(ELISA)分析转化生长因子-β(TGF-β)和白细胞介素-17A(IL-17A)的 mRNA 和蛋白表达水平。实时 PCR 分析叉头框 P3(Foxp3)、维甲酸相关孤儿受体γt(RORγt)和 IL-6 的 mRNA 表达水平。通过 Spearman 相关分析分析 Treg/Th17 比值与这些因子的 mRNA 或蛋白表达水平之间的相关性。数据采用配对 t 检验和独立样本 t 检验进行分析。

结果

感染弓形虫的妊娠小鼠胎盘和脾脏中的 Treg 或 Th17 细胞比例分别显著低于或高于未感染的小鼠。在感染弓形虫的妊娠小鼠胎盘中发现 TGF-β 上调和 IL-17A 下调。与未感染的小鼠相比,感染小鼠的 Treg/Th17 比值显著降低(P<0.01)。Treg/Th17 比值与 TGF-β 蛋白表达水平呈正相关(r=0.6204,P<0.05)或与 IL-17A 蛋白表达水平呈负相关(r=-0.6296,P<0.05)。Treg/Th17 比值与 Foxp3 mRNA 表达水平呈正相关(r=0.7985,P<0.01),与 RORγt mRNA 表达水平呈负相关(r=-0.6153,P<0.05),与 IL-6 mRNA 表达水平呈负相关(r=-0.7492,P<0.01)。

结论

感染弓形虫的妊娠小鼠存在 Treg/Th17 失衡,与相关细胞因子和关键转录因子的表达有关。该结果提示,这种寄生虫引起的胚胎丢失可能与 Treg 与 Th17 细胞数量比值降低有关。

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