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用于研究伯氏疏螺旋体感染的小鼠模型。

Mouse Models for the Study of Borrelia burgdorferi Infection.

机构信息

Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA.

Department of Molecular Microbiology and Immunology, Lyme and Tickborne Diseases Research and Education Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.

出版信息

Curr Protoc. 2024 Aug;4(8):e1127. doi: 10.1002/cpz1.1127.

DOI:10.1002/cpz1.1127
PMID:39193882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11361713/
Abstract

Lyme disease, a tickborne illness caused by Borrelia burgdorferi, is an emerging, significant public health concern. B. burgdorferi infections are challenging to study because of their complex life cycle that requires adaptation to both ticks and mammalian hosts for long-term survival and transmission. Bacterial adaptation is accomplished through extensive gene expression alterations in response to environmental cues that remain to be more fully explored. Mouse models of infection serve as valuable tools for studying B. burgdorferi adaptation to the mammalian host and the spirochete's ability to cause persistent infections and thus to interact with and evade the immune system. This article details three mouse models that differ in their primary methods of infection: infestation with B. burgdorferi infected ticks, intradermal inoculation of culture-grown spirochetes, and infection via subcutaneous transplantation of infected tissue. Each method offers unique advantages and limitations. Tick infestation is the route of natural transmission but presents logistical challenges. Syringe inoculation is easy and provides precise control over the infectious dose, but infection is with culture-adapted bacteria. Transplantation of infected tissue introduces mammalian-host-adapted B. burgdorferi in precise anatomical locations, but misses the transfer of tick factors affecting immunity. Detailed protocols are provided for each of the three infection routes, and pros and cons of each method are outlined to help researchers identify the best approach for a research question to be addressed. A protocol is also provided for the treatment of mice with antibiotics that reliably eliminates detectable spirochetes from the animals. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Syringe inoculation of mice with cultured B. burgdorferi and collection of necropsy tissues Basic Protocol 2: Infection of mice with B. burgdorferi via tick infestation Basic Protocol 3: Infection of mice with host-adapted B. burgdorferi via tissue transplant Support Protocol: Clearance of B. burgdorferi by antibiotic treatment.

摘要

莱姆病是一种由伯氏疏螺旋体引起的蜱传疾病,是一个新出现的、严重的公共卫生问题。由于其复杂的生命周期,需要适应蜱和哺乳动物宿主才能长期生存和传播,因此伯氏疏螺旋体感染的研究具有挑战性。细菌通过对环境线索的广泛基因表达改变来适应,这些环境线索仍有待更充分地探索。感染的小鼠模型是研究伯氏疏螺旋体适应哺乳动物宿主以及螺旋体引起持续性感染的能力,从而与免疫系统相互作用和逃避免疫系统的宝贵工具。本文详细介绍了三种在主要感染方法上有所不同的小鼠模型:感染伯氏疏螺旋体感染的蜱、皮内接种培养的螺旋体和通过皮下移植感染组织进行感染。每种方法都有独特的优点和局限性。蜱感染是自然传播的途径,但存在后勤挑战。注射器接种简单且对感染剂量有精确的控制,但感染的是适应培养的细菌。感染组织的移植将适应哺乳动物宿主的伯氏疏螺旋体引入精确的解剖位置,但错过了影响免疫的蜱因素的转移。为每种感染途径提供了详细的方案,并概述了每种方法的优缺点,以帮助研究人员确定最适合解决研究问题的方法。还提供了一种抗生素治疗小鼠的方案,该方案可可靠地从动物中消除可检测的螺旋体。©2024Wiley Periodicals LLC。基本方案 1:用培养的伯氏疏螺旋体通过注射器接种小鼠并收集尸检组织基本方案 2:通过蜱感染感染小鼠基本方案 3:通过组织移植感染宿主适应的伯氏疏螺旋体小鼠支持方案:抗生素治疗清除伯氏疏螺旋体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f606/11361713/c9951c51c443/nihms-2014485-f0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f606/11361713/adfc8757d273/nihms-2014485-f0002.jpg
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本文引用的文献

1
The Lyme disease spirochete, Borrelia burgdorferi, as a model vector-borne pathogen: insights on regulation of gene and protein expression.莱姆病螺旋体,伯氏疏螺旋体,作为一种模型性的媒介传播病原体:基因和蛋白表达调控的见解。
Curr Opin Microbiol. 2023 Aug;74:102332. doi: 10.1016/j.mib.2023.102332. Epub 2023 Jun 4.
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BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals.BosR 和 PlzA 相互调节 RpoS 功能以维持伯氏疏螺旋体在蜱和哺乳动物中的生存。
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美国卫生与公众服务部蜱传疾病工作组莱姆病发病机制与病理生理学小组委员会报告
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Immune Response to : Lessons from Lyme Disease Spirochetes.对莱姆病螺旋体的免疫反应:教训。
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Clinical spectrum of Lyme disease.莱姆病的临床谱。
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Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion.持续传播与侵袭:莱姆病螺旋体传播与侵袭的综述
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CD4+ T cells promote antibody production but not sustained affinity maturation during Borrelia burgdorferi infection.在伯氏疏螺旋体感染期间,CD4 + T细胞促进抗体产生,但不促进持续的亲和力成熟。
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Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes.论 ticks、mice 和 men:理解莱姆病螺旋体的双重宿主生活方式。
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