Medical & Molecular Sciences, School of Veterinary & Life Sciences, Murdoch University, South Street, Murdoch, Western Australia, 6150, Australia.
School of Medicine, Flinders University, Adelaide, Australia.
J Mol Med (Berl). 2018 Feb;96(2):147-157. doi: 10.1007/s00109-017-1609-2. Epub 2017 Nov 13.
Escherichia coli and Staphylococcus epidermidis are predominant causes of neonatal sepsis, particularly affecting preterm infants. Susceptibility to infection has been attributed to "immature" innate monocyte defences, but no studies have assessed global transcriptional responses of neonatal monocytes to these pathogens. Here, we aimed to identify and characterise the neonatal monocyte transcriptional responses to E. coli and S. epidermidis and the role of common modifiers such as gestational age (GA) and exposure to chorioamnionitis (a common complication of preterm birth) to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (< 32 weeks GA) and term infants (37-40 weeks GA) following standardised challenge with live S. epidermidis or E. coli. The major transcriptional changes induced by either pathogen were highly conserved between infant groups and stimuli, highlighting a common extant neonatal monocyte response to infection, largely mediated by TLR/NF-κB/TREM-1 signalling. In addition, we observed an activated interferon-centred immune response specific to stimulation with E. coli in both preterm and term infants. These data provide novel insights into the functionality of neonatal monocytes at birth and highlight potential pathways that could be targeted to reduce the harmful effects of bacterial-induced inflammation in sepsis. E. coli and S. epidermidis elicit common transcriptional changes in cord monocytes. The common transcriptional response is mediated by TLR/NF-κB/TREM-1 signalling. IFN genes are differentially regulated by E. coli and S. epidermidis in monocytes. These responses are largely unaffected by GA or exposure to chorioamnionitis.
E. coli and S. epidermidis elicit common transcriptional changes in cord monocytes. The common transcriptional response is mediated by TLR/NF-κB/TREM-1 signalling. IFN-genes are differentially regulated by E. coli and S. epidermidis in monocytes. These responses are largely unaffected by GA or exposure to chorioamnionitis.
大肠埃希菌和表皮葡萄球菌是新生儿败血症的主要病原体，尤其是早产儿。感染的易感性归因于“不成熟”的固有单核细胞防御，但尚未有研究评估新生儿单核细胞对这些病原体的全转录组反应。在这里，我们旨在鉴定和描述新生儿单核细胞对大肠埃希菌和表皮葡萄球菌的转录反应，以及常见修饰因子（如胎龄（GA）和暴露于绒毛膜羊膜炎（早产的常见并发症））的作用，以更好地理解生命早期的固有免疫反应。从极早产儿（<32 周 GA）和足月婴儿（37-40 周 GA）的脐血单核细胞中提取纯化的单核细胞，用标准方法分别与活的表皮葡萄球菌或大肠埃希菌孵育，然后进行 RNA 测序。两种病原体诱导的主要转录变化在婴儿组和刺激物之间高度保守，突出了感染后新生儿单核细胞的共同反应，主要由 TLR/NF-κB/TREM-1 信号介导。此外，我们观察到干扰素为中心的免疫反应在早产儿和足月婴儿中均由大肠埃希菌刺激特异性激活。这些数据为新生儿出生时单核细胞的功能提供了新的见解，并强调了可能的途径，这些途径可以被靶向以减少细菌诱导的败血症炎症的有害影响。E. coli 和 S. epidermidis 在脐带血单核细胞中引起共同的转录变化。共同的转录反应由 TLR/NF-κB/TREM-1 信号介导。IFN 基因在单核细胞中受 E. coli 和 S. epidermidis 的差异调节。这些反应在很大程度上不受 GA 或绒毛膜羊膜炎暴露的影响。
