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嗜软骨沃氏菌引起的呼吸道感染小鼠模型

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.

作者信息

Pilloux Ludovic, LeRoy Didier, Brunel Christophe, Roger Thierry, Greub Gilbert

机构信息

Center for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.

Infectious Diseases Service, Department of Medicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland.

出版信息

PLoS One. 2016 Mar 7;11(3):e0150909. doi: 10.1371/journal.pone.0150909. eCollection 2016.

Abstract

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.

摘要

嗜肺瓦罗菌是一种属于衣原体目的专性细胞内细菌,被认为是一种新兴病原体。一些临床研究强调了嗜肺瓦罗菌在细支气管炎、肺炎和流产中可能发挥的作用。嗜肺瓦罗菌能够在人肺细胞、巨噬细胞和子宫内膜细胞内感染并复制,这进一步支持了其致病潜力。鉴于嗜肺瓦罗菌可能是呼吸道感染的病原体,我们建立了一种呼吸道感染小鼠模型,以深入了解嗜肺瓦罗菌的发病机制。经鼻接种2×10⁸嗜肺瓦罗菌后,小鼠体重减轻高达40%,并迅速死于感染,接种后第4天死亡率达到50%。通过qPCR估计,细菌载量在感染后第0天至第3天增加,此后在存活小鼠中下降。通过电子显微镜检测分裂细菌证实了细菌生长,并且在感染后14天从肺中分离出活菌。感染肺组织的免疫组织化学和组织病理学显示存在与肺炎相关的细菌,其特征为重要的多灶性炎症。感染后第3天,肺中高炎症评分与血清和肺中促炎细胞因子的存在相关。该动物模型支持嗜肺瓦罗菌作为呼吸道感染病原体的作用,并将有助于了解这种严格细胞内细菌的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd96/4780729/739bfe3f8602/pone.0150909.g001.jpg

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