Host Defense Against HIV-related Pulmonary Infections

描述（由申请人提供）： 肺部感染是艾滋病毒感染的常见并发症，也是艾滋病患者死亡的常见原因。 合并HIV感染的肺部病原体包括细菌（肺炎）、真菌（卡氏肺孢子虫）和分枝杆菌（结核）。 抗菌治疗对许多这些感染是可能的，但这种治疗在发展中国家可能无法获得，抗生素耐药性是一个日益严重的问题。 解决HIV相关肺部感染问题更直接的方法是纠正HIV感染引起的宿主防御缺陷。该项目的长期目标是确定新的方法来增强HIV感染患者对肺部感染的宿主防御。 在这项申请中，我们将指导和协调一组已建立的宿主防御研究人员进行针对艾滋病毒相关肺部感染的研究。 该项目的主题是探索基因方法，以增强免疫效应细胞进入肺组织，以增加艾滋病毒相关的肺部感染的清除。 我们假设遗传方法可用于增加局部信号，以将免疫效应细胞募集到感染的肺组织中，或增加可用于募集的循环效应细胞库。 四个互动研究项目将涉及： 1. CXCR 3配体作为宿主防御卡氏肺孢子虫中淋巴细胞募集的信号（Shellito博士） 2.肺部感染的CD 4非依赖性疫苗策略（Dr. Kolls） 3.肺结核的初免/加强接种策略（Drs. Ramsay，Mason） 4.增加细菌性肺炎造血反应的策略（Schwarzenberger、纳尔逊和Bagby博士） 研究项目将由3个核心部分支持：行政核心（Shellito博士），免疫学核心（Zhang博士），载体核心（雷泽博士） 项目研究将在与HIV感染相关的肺部感染动物模型中开发和验证免疫增强的新方法。 所产生的数据将为今后应用于艾滋病毒感染者奠定基础。

DESCRIPTION (provided by applicant): Pulmonary infections are frequent complications of HIV infection and a common cause of death in patients with AIDS. Pulmonary pathogens complicating HIV infection include bacteria (pneumonia), fungi (Pneumocystis carinii), and mycobacteria (tuberculosis). Antimicrobial therapy is possible for many of these infections, but such therapies may not be available in developing countries and antibiotic resistance is an increasing problem. A more direct solution to the problem of HIV-related pulmonary infections is to correct the defects in host defense caused by HIV infection. The long-term objective of this Project is to identify new methods to augment host defense against pulmonary infection in HIV-infected patients. In this application, we will direct and coordinate a group of established investigators in host defense to conduct research targeted to HIV-related pulmonary infections. The Project theme is to explore genetic approaches to enhance the delivery of immune effector cells into lung tissue in order to augment clearance of HIV-related pulmonary infections. We postulate that genetic approaches can be used to either increase local signals for recruitment of immune effector cells into infected lung tissue or to increase the pool of circulating effector cells available for recruitment. Four interactive research projects will address: 1. CXCR3 ligands as signals for lymphocyte recruitment in host defense against P. carinii (Dr. Shellito) 2. CD4-independent vaccine strategies for pulmonary infections (Dr. Kolls) 3. Prime/boost vaccination strategies for pulmonary tuberculosis (Drs. Ramsay, Mason) 4. Strategies to increase hematopoietic responses to bacterial pneumonia (Drs. Schwarzenberger, Nelson, and Bagby) The research projects will be supported by 3 core components: Administrative Core (Dr. Shellito), Immunology Core (Dr. Zhang), Vector Core (Dr. Reiser) Project research will develop and validate new methods of immune augmentation in animal models of pulmonary infection relevant to HIV infection. Data generated will then provide a foundation for future applications to HIV-infected patients.