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

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。一种近缘细菌M.avium亚种。副结核(MAP)导致牛的一种慢性衰竭性肠炎，并被认为在人类克罗恩病中起作用。在包括英国和中国在内的许多国家，细菌及其疾病仍然是主要的公共卫生和/或经济问题。在许多国家，牛分枝杆菌感染的发病率有很好的记录，而地图上的信息很少。这两种病原体的混合感染很可能会对两种疾病的进展造成未知的后果。我们利用了一种技术(基于DNA的微阵列)，可以同时检测样本中的许多微生物。我们的检测方法可以同时检测13种分枝杆菌(包括本建议中提到的两种)，这些分枝杆菌将在两个国家应用，以评估单独病原体和混合感染的发病率。一段时间以来，我们还对感染后不久对天然免疫系统的刺激以及相关和无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初始反应，不是后天的反应，而是会以相同的方式对许多不同的细菌类型发生。细胞内细菌在组织中的存在在感染后的一段时间内对无关的病原体具有深刻的抵抗力。这项工作的结果表明，作为一项紧急保护措施，可以使用活细菌疫苗(例如，不会干扰用于测试单个动物和用于监测的标准皮肤试验的活沙门氏菌疫苗)来快速抵抗分枝杆菌感染。有迹象表明，这种方法也可能在某些情况下用于治疗，并有潜在的应用于控制人类感染。该项目将涉及(I)使用dna微阵列技术调查中国和英国的分枝杆菌混合感染和单一分枝杆菌感染的发生率，(Ii)评估感染早期牛分枝杆菌、MAP和沙门氏菌之间的免疫相互作用，以及该方法是否可以用于在幼稚动物可能暴露于感染的时期保护这两种分枝杆菌病原体。

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.