Innate Immunity to Pneumonic Burkholderia Infection

前言：伯克霍尔德氏菌和该属的其他细菌具有作为生物武器的巨大潜力， 然而，关于肺炎伯克霍尔德氏菌感染的发病机制知之甚少。例如，关键效应器 调节伯克霍尔德氏菌天然免疫的细胞或细胞因子以前还没有被研究过。 因此，我们将开发一个肺部感染模型，使我们能够评估先天免疫反应。 致B.马雷。在目标1中，荧光标记的伯克霍尔德氏菌将被用来识别早期的靶细胞 并直接评估对机体的早期先天免疫反应。在目标2中，选择性细胞耗尽 将使用策略来评估肺效应细胞群对生物体控制的影响 无论是局部的还是系统的。最后，在目标3中，我们将评估关键细胞因子和信号传递的作用。 控制伯克霍尔德氏菌复制和肺部病理的先天免疫系统中的分子。 这些研究将提供重要的新信息，对设计新的预防或治疗方案至关重要。 对这种新出现的生物武器制剂的干预。 项目互动：该项目将与其他项目以及 这项提议。这个项目的私人助理是史蒂文·道博士和凯瑟琳·博西奥博士。加州州立大学的施韦泽博士将 充当合作者。核心A(动物模型核心)在Dick Bowen博士的指导下将协助 伯克霍尔德氏菌动物挑战研究的规划和实施。精选代理归档核心(核心 D)将提供马来杆菌的毒力菌株，用于动物挑战实验。施维泽博士将 提供无毒的6株泰兰氏酵母菌株。Schweizer博士(项目2.A.4)还将与我们在 产生绿色荧光蛋白转导的伯克霍尔德氏菌，用于追踪研究。

Introduction: Burkholderia mallei and others in the genus have significant potential for use as bioweapons, yet little is known about the pathogenesis of pneumonic Burkholderia infection. For example, the key effector cells or cytokines regulating innate immunity to Burkholderia have not been previously investigated. Therefore, we will develop a pulmonary infection model that will allow us to assess innate immune responses to B. mallei. In Aim 1, fluorescently-labeled Burkholderia will be used to identify the early target cells in the lung and directly assess early innate immune response to the organism. In Aim 2, selective cell depletion strategies will be used to assess the impact of pulmonary effector cell populations on control of the organism both locally and systemically. Finally, in Aim 3 we will assess the role of key cytokines and signalling molecules in the innate immune system in controlling Burkholderia replication and pulmonary pathology. These studies will provide important new information critical to the design of new prophylactic or therapeutic interventions against this emerging bioweapon agent. Project interactions: This project will coordinate with other projects and with Core Facilities described in this proposal. The Pis of this project are Drs. Steven Dow and Catharine Bosio. Drs. Schweizer at CSU will serve as collaborator. Core A (Animal Models Core) under the direction of Dr. Dick Bowen will assist with the planning and execution of Burkholderia animal challenge studies. The Select Agents Archive Core (Core D) will provide virulent stains of B. mallei for use in animal challenge experiments. Dr. H Schweizer will provide the avirulent 6. thailandensis strains. Dr Schweizer (Project 2.A.4) will also collaborate with us in generating GFP-transduced Burkholderia for use in tracking studies.