Transcriptional analysis of the guinea pig model of tuberculosis

描述（由申请人提供）：本研究的目的是利用微阵列分析更彻底地了解感染豚鼠对结核病的宿主反应，豚鼠被广泛认为是该疾病最相关的小动物模型。利用生物信息学，我们建议在该动物模型中进一步探讨对临床相关的[高/低传播]W-Beijing结核分枝杆菌株和先前接种过疫苗的动物的整体免疫反应的性质。我们特别感兴趣的是进一步研究新疫苗由于在宿主中诱导对高毒力W-Beijing毒株作出反应的调节性T细胞网络而无效的可能性。在过去的一年里，我们的两个合作站点密切合作，解决了关于豚鼠肺RNA分离的各种技术问题，以及运输问题，我们现在有了一个可行的方案来作为这些研究的基础[结果是，一些初步数据]。该计划是在科罗拉多州立大学最先进的生物安全iii级设施中为豚鼠接种疫苗并进行挑战，然后将分离的RNA送到班加罗尔的基因型中心，通过微阵列进行进一步分析。虽然这项技术不再是“新”技术，但这将是第一次在豚鼠模型中进行，也是第一次在疫苗接种和结核病的特定背景下进行[从而使其对美印疫苗行动计划倡议作出高度反应]。因此，在这一重要而相关的动物模型中，它具有很高的潜力提供关于宿主反应的新信息。

DESCRIPTION (provided by applicant): The objective of this study is to use microarray analysis to more thoroughly understand the host response to tuberculosis in infected guinea pigs, widely regarded as the most relevant small animal model of this disease. Using bioinformatics, we propose to further probe the nature of the global immune response in this animal model, both to clinically relevant [high/low transmission] W-Beijing strains of M.tuberculosis, and in animals previously vaccinated. We are specifically interested in further examining the possibility that new vaccines will be ineffective due to the induction in the host of regulatory T cell networks that respond to the highly virulent W-Beijing strains. Over the past year our two collaborative sites have worked together closely to solve a variety of technical problems regarding isolation of guinea pig lung RNA, as well as transport issues, and we now have a workable protocol to base these studies on [and as a consequence, some preliminary data]. The plan is to vaccinate and challenge guinea pigs in the state of the art biosafety level-III facilities at CSU, then send isolated RNA to Genotypic in Bangalore for further analysis by microarray. While this technology is no longer "new" this will be the first time it has been done in the guinea pig model, and the first time in the specific context of vaccination and tuberculosis [thus making it highly responsive to the US-Indo Vaccine Action Program initiative]. As a result, it has high potential to provide new information about the host response in this important and relevant animal model.