沙眼衣原体抗原诱导母体蜕膜细胞 TLR4-TAB1 介导的炎症，但不引起细胞死亡。
Chlamydia trachomatis antigen induces TLR4-TAB1-mediated inflammation, but not cell death, in maternal decidua cells.
机构信息
School of Medicine, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
出版信息
Am J Reprod Immunol. 2023 Mar;89(3):e13664. doi: 10.1111/aji.13664. Epub 2022 Dec 19.
BACKGROUND
During gestation, the decidua is an essential layer of the maternal-fetal interface, providing immune support and maintaining inflammatory homeostasis. Although Chlamydia (C.) trachomatis is associated with adverse pregnancy outcomes the pathogenic effects on maternal decidua contributing to adverse events are not understood. This study examined how C. trachomatis antigen affects cell signaling, cell death, and inflammation in the decidua.
METHODS
Primary decidua cells (pDECs) from term, not-in-labor, fetal membrane-decidua were cultured using the following conditions: (1) control - standard cell culture conditions, (2) 100 ng/ml or (3) 200 ng/ml of C. trachomatis antigen to model decidual cell infection in vitro. Differential expression of Toll-like receptor (TLR) 4 (receptor for C. trachomatis antigen), signaling pathway markers phosphorylated TGF-Beta Activated Kinase 1 (PTAB1), TAB1, phosphorylated p38 mitogen-activated protein kinases (Pp38 MAPK), and p38 MAPK (western blot), decidual cell apoptosis and necrosis (flow cytometry), and inflammation (ELISA for cytokines) were determined in cells exposed to C. trachomatis antigen. T-test was used to assess statistical significance (p < 0.05).
RESULTS
C. trachomatis antigen significantly induced expression of TLR4 (p = 0.03) and activation of TAB1 (p = 0.02) compared to controls. However, it did not induce p38 MAPK activation. In addition, pDECs maintained their stromal cell morphology when exposed to C. trachomatis antigen showing no signs of apoptosis and/or necrosis but did induce pro-inflammatory cytokine interleukin (IL)-6 (100 ng/ml: p = 0.02 and 200 ng/ml: p = 0.03), in pDECs compared to controls.
CONCLUSION
Prenatal C. trachomatis infection can produce antigens that induce TLR4-TAB1 signaling and IL-6 inflammation independent of Pp38 MAPK and apoptosis and necrosis. This suggests that C. trachomatis can imbalance decidual inflammatory homeostasis, potentially contributing to adverse events during pregnancy.
背景
在妊娠期间，蜕膜是母体-胎儿界面的重要一层，提供免疫支持并维持炎症的体内平衡。尽管沙眼衣原体（C.）与不良妊娠结局有关，但导致不良事件的母体蜕膜致病作用尚不清楚。本研究探讨了沙眼衣原体抗原如何影响蜕膜中的细胞信号转导、细胞死亡和炎症。
方法
使用以下条件培养来自足月、非分娩、胎膜-蜕膜的原代蜕膜细胞（pDECs）：（1）对照-标准细胞培养条件，（2）100ng/ml 或（3）200ng/ml 的沙眼衣原体抗原，以模拟体外蜕膜细胞感染。用 Western blot 检测 Toll 样受体（TLR）4（沙眼衣原体抗原的受体）、信号通路标志物磷酸化 TGF-β激活激酶 1（PTAB1）、TAB1、磷酸化 p38 丝裂原活化蛋白激酶（Pp38 MAPK）和 p38 MAPK 的差异表达，用流式细胞术检测蜕膜细胞凋亡和坏死，用 ELISA 检测细胞因子炎症。用 t 检验评估统计学意义（p<0.05）。
结果
与对照组相比，沙眼衣原体抗原显著诱导 TLR4 的表达（p=0.03）和 TAB1 的激活（p=0.02）。然而，它没有诱导 p38 MAPK 的激活。此外，pDECs 在暴露于沙眼衣原体抗原时保持其基质细胞形态，没有凋亡和/或坏死的迹象，但与对照组相比，确实诱导了促炎细胞因子白细胞介素（IL）-6（100ng/ml：p=0.02 和 200ng/ml：p=0.03）的表达。
结论
产前沙眼衣原体感染可产生诱导 TLR4-TAB1 信号和 IL-6 炎症的抗原，而不依赖于 Pp38 MAPK 和凋亡及坏死。这表明沙眼衣原体可能会使蜕膜炎症体内平衡失衡，从而可能导致妊娠期间的不良事件。
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