Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli-infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli-infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.

中文翻译：

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恒河猴早产的诱发取决于对宫内感染的免疫反应强度。

宫内感染/炎症 (IUI) 是早产 (PTL) 的主要原因。然而，IUI 并不一定会导致 PTL。我们假设在有或没有 PTL 的受试者中存在免疫反应的定量和定性差异。为了定义 PTL 的触发因素，我们开发了由脂多糖 (LPS) 或活大肠杆菌驱动的 IUI 恒河猴模型。PTL 没有发生在 LPS 攻击的恒河猴中，而大肠杆菌感染的动物经常早产。尽管 LPS 和活大肠杆菌都引起免疫细胞浸润，但感染大肠杆菌的动物在绒毛膜羊膜蜕膜和羊水 (AF) 中表现出更高水平的炎症介质，尤其是白细胞介素 6 (IL-6) 和前列腺素。绒毛膜蜕膜中的中性粒细胞浸润是 LPS 和大肠杆菌的共同特征。然而，羊膜中的中性粒细胞浸润和 IL6 和 PTGS2 表达由活大肠杆菌特异性诱导。胎儿膜的 RNA 测序 (RNA-seq) 分析显示，与 LPS 相比，大肠杆菌组中参与炎症增强的特定途径，包括 I 型干扰素 (IFN) 反应、趋化性、苏木化和铁稳态被上调团体。我们的数据表明，宿主对 IUI 的免疫反应强度可能决定对 PTL 的易感性。大肠杆菌组与 LPS 组相比。我们的数据表明，宿主对 IUI 的免疫反应强度可能决定对 PTL 的易感性。大肠杆菌组与 LPS 组相比。我们的数据表明，宿主对 IUI 的免疫反应强度可能决定对 PTL 的易感性。