Enhancement of Innate Immunity Against Coxiella Pheumonia

确定应对生物威胁的对策的紧迫性怎么强调都不为过。生物 今天，武器是真实的威胁，“昨天”就需要新的疫苗和其他对策， 帮助保护高风险地区的公众和士兵。疫苗提供了“最好”的对策，但很少 存在许多众所周知的威胁。疫苗的开发是针对特定疾病的;因此， 而用于单一疫苗开发的费用将需要重复用于每种致病性疾病， 剂因此，有必要制定其他对策，这些对策不是针对病原体的， 保护免受广泛的，很多时候，在很大程度上是不可预见的病原体谱-先天性的作用， 免疫系统该项目的重点是确定用于临床的口服佐剂， 对Q热病原体~考克斯/E//布氏杆菌的免疫力。以下假设将在 Toll样受体2（TLR 2）激动剂增加巨噬细胞对C.布梅蒂和增加 体内抗感染。最终的目标是开发出可用于 在治疗上或治疗上增加人对C.布美替尼诱发肺炎。的 将实现以下具体目标。具体目的1：确定TLR 2激动剂对体外杀伤的作用 无毒和毒力C.通过来自抗性和易感小鼠的巨噬细胞对布美替尼进行的研究。具体目标二： 确定TLR 2激动剂或目标1中定义的其他激动剂在增加 巨噬细胞杀伤C.布梅蒂。具体目标3：确定TLR 2激动剂或其他激动剂的作用 在目标1和2下的实验中定义的，关于宿主对无毒力C. 布梅蒂。项目互动：该项目通过参与RCE成为可能，并直接涉及 Harmsen博士在宿主/病原体相互作用方面所做的工作，Minnick博士在细菌相互作用方面所做的工作。 发病机制和帕斯夸尔博士对疫苗开发。它还补充了辅助治疗方面的努力 肺病毒感染正在追求在USU和先天宿主反应的研究， 伯克霍尔德氏菌在鉴证科做该项目还将涉及与细菌学的广泛互动 CORE A.

The urgency in identifying countermeasures against biologic threats cannot be overstated. Biological weapons are real threats today and new vaccines and other countermeasures were needed "yesterday" to help protect the public and soldiers in high-risk areas. Vaccines offer the "best" countermeasure, but few exist for many of the well-known threats. The development of vaccines is disease specific; thus, the time and expense spent on a single vaccine development will need to be repeated for each disease-causing agent. As such, there is a need to develop other countermeasures that are not disease-agent specific and protect against a broad and, many times, largely unforeseen spectrum of pathogens-the role of the innate immune system. This project is focused on identifying for clinical use, oral adjuvants that enhance innate immunity against the causative agent of Q-fever~Cox/e//a bumetii. The following hypothesis will be tested in this project: toll-like receptor 2 (TLR2) agonists increase macrophage killing of C. bumetii and increase resistance to infection in vivo. The ultimate goal is to develop orally active adjuvants that can be used therapeutically or prophylactically to increase human resistance to C. bumetii induced pneumonia. The following specific aims will be pursued. Specific Aim 1: Determine effect of TLR2 agonists on in vitro killing of avirulent and virulent C. bumetii by macrophages from resistant and susceptible mice. Specific Aim 2: Determine mechanism of action of TLR2 agonists, or other agonists defined in Aim 1, in increasing macrophage killing of C. bumetii. Specific Aim 3: Determine effect of TLR2 agonist, or other agonists defined in the experiments under Aims 1 and 2, on host resistance to in vivo challenge with avirulent C. bumetii. Project interactions: This project is made possible by participation in the RCE and involves direct interactions with the work being done by Dr. Harmsen on host/pathogen interactions, Dr. Minnick on bacterial pathogenesis and Dr. Pascual on vaccine development. It also complements the efforts on adjuvant therapy for pulmonary virus infections being pursued at USU and the studies of innate host responses against Burkholderia being done at CSU. This projects will also involve extensive interactions wjth the bacteriology CORE A.