Chronic Tuberculosis: Latent or Dynamic

描述(由申请人提供)：科罗拉多州立大学分枝杆菌研究实验室的这份提案是对AI-44072项目的竞争性更新，“慢性结核病：潜伏的还是动态的？”在上一个供资期间，它在每一项目标方面都取得了实质性进展。在这项新的提案中，我们希望继续尝试定义控制和维持慢性病状态完整性的免疫学机制，我们相信这最终将提供对人类潜伏性结核病基础的更好理解。在这项建议中，第一个目标是更好地确定IL-10的作用，并确定其在易发生这一事件的小鼠品系的再激活疾病中的潜在作用。第二个目标是继续我们对CD8T细胞在慢性病状态中的作用的研究，因为越来越多的证据表明，它们在维持这一过程的完整性方面发挥了重要作用。第三个目标是利用最近在MRL建立的一个新的微阵列实验室。利用这一设施，我们打算尝试提供随着肺部免疫反应从遏制发展到慢性疾病状态的基因表达的全球图景[最初集中在细胞因子、趋化因子及其受体上]。最后，在第四个目标中，我们建议继续开发新的动物模型，以提供关于慢性/潜伏性结核病的新信息。拟议的工作将利用CSU先进的生物安全III级设施、CSU分枝杆菌研究实验室各成员的广泛专业知识以及一些高素质的顾问合作者。

DESCRIPTION (provided by applicant): This proposal from the Mycobacteria Research Laboratories, Colorado State University, is for competitive renewal of program AI-44072, "Chronic tuberculosis: latent or dynamic?" which in the previous funding period has made substantial progress in each of its Aims. In this new proposal, we wish to continue to try to define the immunological mechanisms that control and maintain the integrity of the chronic disease state, which we believe will ultimately provide a better understanding of the basis of latent tuberculosis in humans. In this proposal the first objective is to better define the role of IL-10, and to determine its potential role in reactivation disease in mouse strains prone to this event. The second Aim is to continue our studies on the role of CD8 T cells during the chronic disease state, given the accumulating evidence that they play an important role in maintaining the integrity of this process. A third Aim takes advantage of a new microarray laboratory recently established in the MRL. Using this facility we intend to try to provide a global picture of gene expression [concentrating initially on cytokines, chemokines, and their receptors] as the immune response in the lungs develops from containment, through the chronic disease state. Finally, in a fourth Aim, we propose to continue to develop new animal models that may provide new information about chronic/latent tuberculosis. The proposed work will take advantage of the advanced biosafety level III facilities at CSU, the broad expertise of various members of the Mycobacteria Research Laboratories, CSU, as well as a number of highly qualified consultants collaborators.