Immunopathogenesis of Coxiella pneumonia

由于贝氏柯克斯体是一种很难处理的生物体， Q热肺炎免疫发病机制然而，从这一领域所做的少量工作来看， 从已知的对其他细胞内细菌的免疫反应来看，我们假设T1- 与T细胞反应一样，产生IFN-γ，清除肺部已建立的柯克斯体感染， 此外，肺中的局部免疫球蛋白反应可以帮助宿主抵抗感染的起始 在气溶胶暴露于病原体之后。为了解决这个假设，我们建议：1。来定义细胞 和体液宿主免疫应答，并与原发性和继发性柯克斯体感染相关， 宿主反应与柯克斯体生长和清除动力学; 2.以确定细胞和体液 机制负责主要和次要（记忆）的阻力，考克斯，3。以确定 粘膜免疫是否比全身免疫更有效地产生长期 对柯克斯体有效免疫从这里提出的研究结果将导致更好地了解 Coxiella pneumonia的免疫发病机制这些知识对于合理设计 免疫疗法对抗这种感染。 项目互动：该项目（项目3）将提供从感染小鼠中分离的第1阶段Coxiella， 项目1用于基因表达分析。该项目的成果将与项目2和项目4共享 世卫组织在制定疫苗时会考虑这些因素。项目3还将与项目2密切合作， 候选佐剂功效的体内测试的性能。同样，项目3将工作 在确定候选疫苗构建体和递送系统的功效方面与项目4密切相关。最后， 来自项目1的关于Coxiella如何响应宿主的结果对于理解宿主如何 Coxiella（项目1）。

Because Coxiella burnetii is such a difficult organism to work with, there is little known about the immunopathogenesis of Q fever pneumonia. Howeveer, from the little work that has been done in this area and from what is known about immune responses to other intracellular bacteria, we hypothesize that a T1- like T cell response, with the production of IFN-y, clears established Coxiella infection from the lung and, in addition, that a local immunoglobulin response in the lung can help the host to resist the initiation of infection after aerosol exposure to the pathogen. To address this hypothesis we propose to: 1. to define the cellular and humoral host immune responses to both primary and secondary Coxiella infection and to correlate the host response with the kinetics of Coxiella growth and clearance; 2. to determine the cellular and humoral mechanisms responsible for primary and secondary (memory) resistance to Coxiella', 3. to determine whether mucosal immunization is more effective than systemic immunization in generating long term effective immunity to Coxiella. Results from the studies proposed here will lead to a better understanding of the immunopathogenesis of Coxiella pneumonia. Such knowledge is crucial to the rational design of immunotherapies against this infection. Project Interactions: This project (Project 3) will supply phase 1 Coxiella isolated from infected mice to Project 1 for the analysis of gene expression. The results of this project will be shared with Projects 2 and 4 who will consider them in the formulation of their vaccines. Project 3 will also work closely with Project 2 in the performance of the in vivo testing of the efficacy of candidate adjuvants. Similarly, Project 3 will work closely with Project 4 in determining efficacy of candidate vaccine constructs and delivery systems. Lastly, results from Project 1 on how Coxiella responds to the host will be important in understanding how the host responds to Coxiella (Project 1).