Abstract：
Infection by Coxiella burnetii, the etiological agent of Q fever, poses the risk of causing severe obstetrical complications in pregnant women. C. burnetii is known for its placental tropism based on animal models of infection. The Nine Mile strain has been mostly used to study C. burnetii pathogenicity but the contribution of human isolates to C. burnetii pathogenicity is poorly understood. In this study, we compared five C. burnetii isolates from human placentas with C. burnetii strains including Nine Mile (NM) as reference. Comparative genomic analysis revealed that the Cb122 isolate was distinct from other placental isolates and the C. burnetii NM strain with a set of unique genes involved in energy generation and a type 1 secretion system. The infection of Balb/C mice with the Cb122 isolate showed higher virulence than that of NM or other placental isolates. We evaluated the pathogenicity of the Cb122 isolate by in vitro and ex vivo experiments. As C. burnetii is known to infect and survive within macrophages, we isolated monocytes and placental macrophages from healthy donors and infected them with the Cb122 isolate and the reference strain. We showed that bacteria from the Cb122 isolate were less internalized by monocyte-derived macrophages (MDM) than NM bacteria but the reference strain and the Cb122 isolate were similarly internalized by placental macrophages. The Cb122 isolate and the reference strain survived similarly in the two macrophage types. While the Cb122 isolate and the NM strain stimulated a poorly inflammatory program in MDM, they elicited an inflammatory program in placenta macrophages. We also reported that the Cb122 isolate and NM strain were internalized by trophoblastic cell lines and primary trophoblasts without specific replicative profiles. Placental explants were then infected with the Cb122 isolate and the NM strain. The bacteria from the Cb122 isolate were enriched in the chorionic villous foetal side. It is likely that the Cb122 isolate exhibited increased virulence in the multicellular environment provided by explants. Taken together, these results showed that the placental isolate of C. burnetii exhibits a specific infectious profile but its pathogenic role is not as high as the host immune response in pregnant women.
摘要：
伯氏柯西氏菌感染，Q热的病因，孕妇有可能导致严重的产科并发症。根据感染的动物模型，布氏梭菌以其胎盘嗜性而闻名。九里菌株主要用于研究C.burnetii致病性，但人类分离株对C.burnetii致病性的贡献知之甚少。在这项研究中,我们比较了来自人类胎盘的5株C.burnetii分离株与包括九里（NM）的C.burnetii菌株作为参考。比较基因组分析显示，Cb122分离株与其他胎盘分离株和伯氏芽孢杆菌NM菌株不同，具有一组参与能量产生和1型分泌系统的独特基因。用Cb122分离株感染Balb/C小鼠显示出比NM或其他胎盘分离株更高的毒力。我们通过体外和离体实验评估了Cb122分离物的致病性。由于已知C.burnetii感染并在巨噬细胞中存活，我们从健康供体中分离出单核细胞和胎盘巨噬细胞，并用Cb122分离株和参考菌株感染它们。我们表明，与NM细菌相比，来自Cb122分离株的细菌被单核细胞衍生的巨噬细胞（MDM）内化较少，但参考菌株和Cb122分离株被胎盘巨噬细胞类似地内化。Cb122分离株和参考菌株在两种巨噬细胞类型中类似地存活。虽然Cb122分离株和NM菌株在MDM中刺激了不良的炎症程序，他们在胎盘巨噬细胞中引发了炎症程序。我们还报道了Cb122分离株和NM菌株被滋养细胞系和原代滋养细胞内化，没有特定的复制特征。然后用Cb122分离株和NM菌株感染胎盘外植体。来自Cb122分离物的细菌富集在绒毛膜绒毛胎儿侧。Cb122分离株可能在外植体提供的多细胞环境中表现出增加的毒力。一起来看,这些结果表明，胎盘分离株具有特定的感染特征，但其致病作用不如孕妇的宿主免疫反应高。
