Medical & Molecular Sciences, School of Veterinary & Life Sciences, Murdoch University, Perth, Australia.
School of Medicine, Flinders University, Adelaide, Australia.
Immunol Cell Biol. 2018 Sep;96(8):792-804. doi: 10.1111/imcb.12037. Epub 2018 Apr 23.
Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens.
早产儿极易发生迟发性败血症，而这种败血症通常由皮肤共生菌表皮葡萄球菌引起。先天免疫反应，尤其是单核细胞的免疫反应，是一种关键的保护机制。早产儿单核细胞产生细胞因子的能力受损已得到充分描述，但很少有研究全面评估相应的单核细胞转录反应。早产儿的先天免疫反应可能受到炎症的调节，例如产前存在组织学绒毛膜羊膜炎，这种炎症会使 40%-70%的早产儿发病。绒毛膜羊膜炎改变了迟发性败血症的风险，但它对单核细胞功能的影响在很大程度上尚不清楚。在这里，我们旨在通过流式细胞术确定接触绒毛膜羊膜炎对脐血单核细胞的比例和表型的影响，以及它们对活表皮葡萄球菌的转录反应。对来自极早产儿（<32 周妊娠，有或没有绒毛膜羊膜炎暴露）和足月婴儿（37-40 周妊娠）的脐血单核细胞进行了 RNA-seq 分析，这些婴儿在接受活表皮葡萄球菌预挑战和后挑战之前和之后。与足月婴儿相比，没有接触绒毛膜羊膜炎的早产儿单核细胞对表皮葡萄球菌的固有转录反应并没有表现出缺陷。相比之下，绒毛膜羊膜炎暴露与一组涉及抗原呈递和适应性免疫的基因的低反应性转录表型有关。总的来说，我们的研究结果表明，产前炎症暴露可能通过调节单核细胞对病原体的反应，部分改变早产儿败血症的风险。
