Innate Immunity to Pneumonic Burkholderia Infection

简介：鼻疽伯克霍尔德菌和该属的其他细菌具有用作生物武器的巨大潜力， 然而，对肺炎伯克霍尔德氏菌感染的发病机理知之甚少。例如，关键效应器 调节对伯克霍尔德氏菌的先天免疫的细胞或细胞因子以前没有研究过。 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 到B。鼻疽在目标1中，荧光标记的伯克霍尔德氏菌将被用于鉴定在细胞中的早期靶细胞。 肺，并直接评估对生物体的早期先天免疫反应。在目标2中，选择性细胞耗竭 策略将用于评估肺效应细胞群体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导的作用。 天然免疫系统中的分子在控制伯克霍尔德氏菌复制和肺部病理中的作用。 这些研究将为设计新的预防或治疗药物提供重要的新信息。 对这种新出现的生物武器进行干预。 项目互动：本项目将与其他项目以及 这个提议。这个项目的PI是史蒂文·道博士和凯瑟琳·博西奥博士。鉴证科的施韦泽医生 作为合作者。核心A（动物模型核心）将在Dick Bowen博士的指导下协助 伯克霍尔德菌动物攻毒研究的规划和执行。Select Agents Archive Core（核心 D）将提供B的毒力菌株。用于动物攻击实验的鼻疽。H Schweizer博士将 提供无毒6. thailandensis strains. Schweizer博士（项目2.A.4）也将与我们合作， 产生GFP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.