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 effectorcells 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 responsesto B. mallei.
In Aim 1, fluorescently-labeled Burkholderia will be used to identify the early target cells in thelung and directly assess early innate immune response to the organism.
In Aim 2, selective cell depletionstrategies will be used to assess the impact of pulmonary effector cell populations on control of the organismboth locally and systemically. Finally, in Aim 3 we will assess the role of key cytokines and signallingmolecules 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 therapeuticinterventions against this emerging bioweapon agent.Project interactions: This project will coordinate with other projects and with Core Facilities described inthis proposal. The Pis of this project are Drs. Steven Dow and Catharine Bosio. Drs. Schweizer at CSU willserve as collaborator. Core A (Animal Models Core) under the direction of Dr. Dick Bowen will assist withthe planning and execution of Burkholderia animal challenge studies. The Select Agents Archive Core (CoreD) will provide virulent stains of B. mallei for use in animal challenge experiments. Dr. H Schweizer willprovide the avirulent 6. thailandensis strains. Dr Schweizer (Project 2.A.4) will also collaborate with us ingenerating GFP-transduced Burkholderia for use in tracking studies.
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