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Pulmonary innate immunity and pathogens of the order Actinomycetales

肺部先天免疫和放线菌目的病原体

基本信息

批准号：
8092783
负责人：
TRACY K CARLSON
金额：
$ 11.5万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8092783
关键词：
Acquired Immunodeficiency Syndrome Actinomycetales Air Alveolar Alveolar Macrophages Alveolus Anatomy Antimicrobial Effect Bacteria Bathing Binding Biology Biomedical Research Breathing Carbohydrates Cause of Death Cells Chemotaxis Communicable Diseases Complex Core Facility Data Disease Disease Outcome Doctor of Philosophy Economics Eligibility Determination Employment Environment Epithelial Cells Equus caballus Faculty Fostering Gases Gene Expression Genus Mycobacterium Growth Histopathology Immune Immune response Immune system Immunocompromised Host Immunotherapy Industry Infection Inflammation Inositol Investigation K-Series Research Career Programs Laboratories Licensing Life Liquid substance Lung Lung diseases Mannose Mediating Medicine Mentors Modeling Modification Morbidity - disease rate Mus Mutation Mycobacterium smegmatis Mycobacterium tuberculosis Natural Immunity Ohio Opportunistic Infections Organ Outcome Particulate Matter Pathogenesis Pathology Patients Pattern Phagocytosis Phospholipids Population Positioning Attribute Prevalence Principal Investigator Production Property Proteins Pulmonary Surfactant-Associated Protein A Pulmonary Surfactant-Associated Protein D Pulmonary alveolar structure Research Research Personnel Research Proposals Resistance Respiratory Tract Infections Rhodococcus Rhodococcus equi Scientist Source Students Surface Surface Tension Testing Tissues Training Training Programs Training Support Tuberculosis Universities Veterinarians Veterinary Medicine Virulence Virulent World Health aerosolized bactericide cell envelope college cytokine experience in vitro Assay in vivo insight lipoarabinomannan macrophage microbial migration monocyte neutrophil novel strategies pathogen prevent public health relevance receptor respiratory response statistics surfactant

项目摘要

DESCRIPTION (provided by applicant): THE CANDIDATE: Dr. Tracy Carlson, a licensed veterinarian with board-eligibility in veterinary anatomic pathology, is completing a Ph.D. training program at the Ohio State University (OSU). The K01 SERCA will support her training and progression to scientific independence. THE ENVIRONMENT: OSU has an extensive biomedical research complex including state of the art core facilities in the Colleges of Medicine / Veterinary Medicine. Dr. Larry Schlesinger, the Principal Investigator's mentor, is the Director of both the Infectious Disease Division and the Center for Microbial Interface Biology. Dr. Schlesinger is an experienced mentor in the training of Ph.D. students and K award trainees. THE TRAINING PLAN: The first year of the K award will be used to support the completion of the Ph.D. training of Dr. Carlson in a mentored environment in Dr. Schlesinger's laboratory. The last four years will be used to facilitate Dr. Carlson's transition to an independent researcher following the plan outlined in the research proposal. This will foster eligibility for employment in competitive staff and faculty scientist positions. THE RESEARCH: The initial interaction of respiratory pathogens with the innate immune system is critical for determining the outcome of disease particularly for bacteria of the order Actinomycetales, such as Mycobacteria and Rhodococcus spp., which have the ability to live in innate immune cells (alveolar macrophages). Interaction of the local lung environment, in particular surfactant protein D, has antimicrobial effects on Mycobacterium tuberculosis in in vitro assays. In this research proposal we will further define the interaction of SP-D with M. tuberculosis and the effect it has on the survival of the bacteria in in vitro assays and in vivo in part by exploring the effect of SP-D mutations on the outcome of infection. Additional research will focus on the pulmonary host response to the related Rhodococcus equi, a bacterium that is a significant source of opportunistic pulmonary disease in immunocompromised (AIDS) patients as well as being an important cause of economic loss and morbidity as a disease of young horses. Defining and modulating the interaction of the pulmonary environment with these pathogens will open new avenues of investigation into potential targeted immunotherapies. PUBLIC HEALTH RELEVANCE: Tuberculosis is one of the leading causes of death due to a single infectious disease agent and infects ~ 1/3 of the world's population. The related Rhodococcus equi is an opportunistic infection in AIDS patients and a cause of economic loss / morbidity in the equine industry. Our project will define the initial interaction of these bacteria with the lung innate immune system and generate novel approaches to immunotherapy.

描述（由申请人提供）：候选人：Tracy Carlson博士，一名具有兽医解剖病理学委员会资格的执业兽医，正在完成博士学位。在俄亥俄州州立大学（OSU）的培训计划。K 01 SERCA将支持她的培训和科学独立的发展。环境：俄勒冈州立大学拥有广泛的生物医学研究综合体，包括医学/兽医学院的最先进的核心设施。Larry Schlesinger博士是主要研究者的导师，是传染病部和微生物界面生物学中心的主任。施莱辛格博士是一位经验丰富的博士培训导师。学生和K奖学员。培训计划：K奖的第一年将用于支持博士学位的完成。在施莱辛格博士实验室的指导环境中对卡尔森博士进行培训。最后四年将用于促进卡尔森博士按照研究提案中概述的计划向独立研究员过渡。这将提高在有竞争力的教职员工和科学家职位上就业的资格。研究：呼吸道病原体与先天免疫系统的初始相互作用对于确定疾病的结果是至关重要的，特别是对于放线菌目的细菌，如分枝杆菌和红球菌属，其具有在先天免疫细胞（肺泡巨噬细胞）中生存的能力。局部肺环境的相互作用，特别是表面活性蛋白D，在体外试验中对结核分枝杆菌具有抗菌作用。在本研究中，我们将进一步确定SP-D与M的相互作用。结核病及其在体外测定中对细菌存活的影响，以及部分通过探索SP-D突变对感染结果的影响在体内进行。其他研究将集中在肺宿主对相关马红球菌的反应，马红球菌是免疫功能低下（艾滋病）患者机会性肺病的重要来源，也是经济损失和年轻马匹发病的重要原因。定义和调节肺部环境与这些病原体的相互作用将为潜在的靶向免疫治疗开辟新的研究途径。公共卫生相关性：结核病是由单一传染病病原体引起的主要死亡原因之一，感染了世界人口的约1/3。相关的马红球菌是艾滋病患者的机会性感染，也是马产业经济损失/发病的原因。我们的项目将定义这些细菌与肺部先天免疫系统的初始相互作用，并产生新的免疫治疗方法。