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活体生物发光成像:改良鼠型溃疡分枝杆菌尾模型的工具。

In Vivo Imaging of Bioluminescent : A Tool to Refine the Murine Buruli Ulcer Tail Model.

机构信息

Department of Internal Medicine/Infectious Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.

出版信息

Am J Trop Med Hyg. 2019 Dec;101(6):1312-1321. doi: 10.4269/ajtmh.18-0959.

Abstract

Buruli ulcer (BU) is a neglected tropical disease caused by infection with . Unclear transmission, no available vaccine, and suboptimal treatment regimens hamper the control of this disease. Carefully designed preclinical research is needed to address these shortcomings. In vivo imaging (IVIS, Perkin Elmer, Waltham, MA) of infection is an emerging tool that permits monitoring of disease progression and reduces the need to using large numbers of mice at different time-points during the experiment, as individual mice can be imaged at multiple time-points. We aimed to further describe the use of in vivo imaging (IVIS) in BU. We studied the detection of in experimentally infected BALB/c mouse tails and the subsequent histopathology and immune response in this pilot study. IVIS-monitoring was performed weekly in ten infected BALB/c mice to measure light emitted as a proxy for bacterial load. Nine of 10 (90%) BALB/c mice infected subcutaneously with 3.3 × 10 JKD8049 (containing pMV306 hsp16+luxG13) exhibited light emission from the site of infection, indicating growth in vivo, whereas only five of 10 (50%) animals developed clinical signs of the disease. Specific antibody titers were detected within 2 weeks of the infection. Interferon (IFN)-γ and interleukin (IL)-10 were elevated in animals with pathology Histopathology revealed clusters of acid-fast bacilli in the subcutaneous tissue, with macrophage infiltration and granuloma formation resembling human BU. Our study successfully showed the utility of IVIS monitoring and lays a foundation for further research.

摘要

布鲁里溃疡(BU)是一种由 感染引起的被忽视的热带病。传播途径不明确、没有可用的疫苗和治疗方案不理想,这都阻碍了该疾病的控制。需要精心设计临床前研究来解决这些不足。体内成像(IVIS,Perkin Elmer,Waltham,MA)是一种新兴的工具,可以监测疾病的进展,减少在实验过程中在不同时间点使用大量小鼠的需要,因为可以在多个时间点对单个小鼠进行成像。我们旨在进一步描述体内成像(IVIS)在 BU 中的应用。我们研究了在实验性感染 BALB/c 小鼠尾部时对 的检测,以及在这项初步研究中随后的组织病理学和免疫反应。每周对 10 只感染的 BALB/c 小鼠进行 IVIS 监测,以测量作为细菌载量替代物发射的光。用 3.3×10 JKD8049(含有 pMV306 hsp16+luxG13)皮下感染的 10 只 BALB/c 小鼠中有 9 只(90%)在感染部位发出光,表明体内 生长,而 10 只动物中有 5 只(50%)出现疾病的临床症状。在感染后 2 周内检测到特异性抗体滴度。具有病理学的动物中干扰素(IFN)-γ和白细胞介素(IL)-10 升高。组织病理学显示,在皮下组织中有抗酸杆菌簇,有巨噬细胞浸润和肉芽肿形成,类似于人类 BU。我们的研究成功地展示了 IVIS 监测的实用性,并为进一步研究奠定了基础。

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