CUKPGP: Epidemio- and immunological perspectives and prophylactic potential of Mycobacterium bovis and M. paratuberculosis co-infections in cattle

CUKPGP：牛分枝杆菌和副结核分枝杆菌混合感染的流行病学和免疫学观点以及预防潜力

• 批准号: BB/L004364/1
• 负责人: Paul Barrow
• 金额: $ 25.72万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL004364%2F1
• 关键词: CUKPGP; Epidemio; immunological; perspectives; prophylactic

Mycobacterium bovis, a relative of the bacterium causing human tuberculosis is the causative agent of bovine tuberculosis. A related bacterium M. avium subsp. paratuberculosis (MAP) causesa chronic wasting enteritis in cattle and is thought to have a role in Crohn's disease in man. Bothbacteria and thier diseases remain major public health and/or economic problems in many countries, including the UK and P.R.China. The incidence of M. bovis infection is well documented whereas information on MAP is poor in many countries. It is likely that mixed infection with these two pathogens occurs with unknown consequences for the progress of both diseases. We have exploited a technology (a DNA-based microarray) that allows simultaneous detection of many micro-organisms in a sample simultaneously. Our assay allows the simultaneous detection of 13 mycobacterial species (including the two mentioned in this proposal), which will be applied in both countries to assess the incidence of infection with the individual pathogens and also of mixed infection.We have also been interested for some time in the stimulation of the innate immune system shortly after infection and the consequences for subsequent infection by related and unrelated pathogens. Innate immunity is the initial host response to infection an is not a learned response but will occur in the same way to many different bacterial types. The presence of intracellular bacteria in the tissues confers a profound resistance for some time after infection against unrelated pathogens. The outcome of this work is the indication that live bacterial vaccines (e.g. live Salmonella vaccines which would not interfere with the standard skin test used for testing individual animals and for surveillance) might be used to confer rapid resistance to mycobacterial infection as an emergency protection measure. There is an indication that this approach might also be used therapeutically in some circumstances and has potential application for controlling human infection..This project will involve (i) use of DNA microarray technology to survey the incidence of mixed and single mycobacterial infections in China and the UK, and (ii) an assessment of the immunological interaction between M. bovis, MAP and Salmonella early in infection and whether this approach might be used to protect against these two mycobacterial pathogens for periods when naïve animals might be exposed to infection.

牛分枝杆菌是引起人类结核病的细菌的近亲，是牛结核病的病原体。一个相关的细菌M.鸟亚种副结核杆菌（MAP）引起牛的慢性消耗性肠炎，并被认为与人的克罗恩病有关。在包括英国和中国在内的许多国家，这两种细菌及其疾病仍然是主要的公共卫生和/或经济问题。M.牛的感染有详细的记录，而在许多国家，关于MAP的信息很少。这两种病原体的混合感染很可能对两种疾病的进展产生未知的后果。我们开发了一种技术（基于DNA的微阵列），可以同时检测样品中的许多微生物。我们的检测方法可以同时检测13种分枝杆菌（包括本提案中提到的两种），这将在两个国家应用，以评估单个病原体感染和混合感染的发生率。我们还对感染后不久先天免疫系统的刺激以及相关和不相关病原体随后感染的后果感兴趣。先天免疫是宿主对感染的最初反应，不是习得性反应，但对许多不同的细菌类型也会以同样的方式发生。组织中细胞内细菌的存在赋予了对不相关病原体感染后一段时间的深刻抵抗力。这项工作的结果表明，活细菌疫苗（例如，不会干扰用于测试个体动物和监测的标准皮肤试验的沙门氏菌活疫苗）可用于赋予对分枝杆菌感染的快速抵抗力，作为紧急保护措施。有迹象表明，这种方法也可以在某些情况下用于治疗，并具有控制人类感染的潜在应用。本项目将包括（i）使用DNA微阵列技术调查中国和英国混合和单一分枝杆菌感染的发病率，以及（ii）评估分枝杆菌之间的免疫相互作用。牛，MAP和沙门氏菌感染早期，以及这种方法是否可以用来防止这两种分枝杆菌病原体的时期，当天真的动物可能暴露于感染。