Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland.
Department of Women's and Children's Health Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Sci Rep. 2019 Apr 11;9(1):5920. doi: 10.1038/s41598-019-42551-w.
Preeclampsia is a multisystemic disorder leading to the development of a placental ischemic microenvironment with a resultant increase in oxidative stress. There is evidence that mitochondrial dysfunction and the innate immune system both play a role in the pathophysiology of this disease. Mitochondrial DAMPs such as mtDNA bind specific pattern recognition receptors such as Toll-like receptor 9 (TLR9) on the endosomal surface of immune cells, in particular neutrophils, subsequently activating them and triggering an innate response. We hypothesised that the exaggerated innate immune response seen in preeclampsia is provoked by dysfunctional mitochondria. Here we provide evidence that TLR9 activity is significantly increased at time of disease in women with preeclampsia. Furthermore, we show activation of neutrophil markers, Calprotectin, Myeloperoxidase (MPO), and IL-8 are significantly increased at time of disease compared to uncomplicated pregnancies. This research supports a potential role of TLR9 activation of an innate immune response evident in preeclampsia which may possibly be initially triggered by dysfunctional mitochondria.
子痫前期是一种多系统疾病，导致胎盘缺血性微环境的发展，从而导致氧化应激增加。有证据表明，线粒体功能障碍和固有免疫系统都在这种疾病的病理生理学中发挥作用。线粒体 DAMPs（如 mtDNA）与免疫细胞（特别是中性粒细胞）的内体表面上的特定模式识别受体（如 Toll 样受体 9（TLR9）结合，随后激活它们并触发固有反应。我们假设子痫前期中所见的过度固有免疫反应是由功能失调的线粒体引起的。在这里，我们提供的证据表明，患有子痫前期的女性在疾病发作时 TLR9 活性显着增加。此外，与正常妊娠相比，我们发现中性粒细胞标志物 Calprotectin、髓过氧化物酶（MPO）和 IL-8 的活性在疾病发作时显着增加。这项研究支持 TLR9 激活固有免疫反应在子痫前期中的潜在作用，这种作用可能最初是由功能失调的线粒体触发的。
