Immunopathogenesis of Coxiella pneumonia

由于伯氏柯克斯体是一种很难处理的生物，人们对它知之甚少 Q热肺炎的免疫发病机制。然而，从这一领域所做的少量工作来看， 根据已知的对其他细胞内细菌的免疫反应，我们假设T1- 与T细胞反应一样，通过产生干扰素-γ，清除肺部已确立的柯克斯体感染，并在 此外，肺部的局部免疫球蛋白反应可以帮助宿主抵抗感染的开始 在气雾剂暴露于病原体之后。为了解决这一假设，我们建议：1.定义细胞 和体液宿主对原发和继发柯克斯体感染的免疫反应，并与 宿主反应与柯克斯体生长和清除的动力学；2.测定细胞和体液 柯克斯体原发和继发(记忆)抵抗的机制，3.确定 粘膜免疫是否比系统免疫更有效地产生长期效应 对柯克斯氏菌有效免疫。这里提出的研究结果将使我们更好地理解 柯克斯体肺炎的免疫发病机制。这些知识对于合理的设计是至关重要的 针对这种感染的免疫疗法。 项目互动：该项目(项目3)将提供从受感染的小鼠身上分离的第一期柯克斯体 关于基因表达分析的项目1。该项目的成果将与项目2和项目4共享 世卫组织将在其疫苗的配方中考虑它们。项目3还将在年与项目2密切合作 体内性能测试候选佐剂的疗效。同样，项目3也会起作用 在确定候选疫苗构造和递送系统的有效性方面与项目4密切相关。最后， 项目1关于柯克斯体如何回应宿主的结果将对理解宿主如何 回应柯克斯拉病毒(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).