Pulmonary innate immunity and pathogens of the order Actinomycetales

肺部先天免疫和放线菌目病原体

• 批准号: 8284436
• 负责人: TRACY K CARLSON
• 金额: $ 3.41万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284436
• 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

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：特雷西·卡尔森（Tracy Carlson）博士是一名有执照的兽医，董事会有资格获得兽医解剖病理学，正在填写博士学位。俄亥俄州立大学（OSU）的培训计划。 K01 SERCA将支持她的训练和发展至科学独立性。环境：OSU拥有广泛的生物医学研究综合体，包括医学 /兽医学院中最先进的核心设施。主要研究者的导师Larry Schlesinger博士是传染病部和微生物界面生物学中心的主任。 Schlesinger博士是培训博士学位的经验丰富的导师。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，对卡尔森博士的培训。在研究建议中概述的计划之后，过去四年将用于促进卡尔森博士向独立研究人员的过渡。这将培养有资格在有竞争力的员工和教师科学家职位上就业。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局至关重要，特别是对于诸如分枝杆菌和杜鹃花spp的细菌的细菌，它们具有生活在先天免疫细胞中的能力（肺泡巨摩托杆）。局部肺部环境的相互作用，特别是表面活性剂蛋白D，在体外测定中对结核分枝杆菌具有抗菌作用。在这项研究建议中，我们将进一步定义SP-D与结核分枝杆菌的相互作用及其对细菌在体外测定和体内生存的影响，部分原因部分是通过探索SP-D突变对感染结果的影响。进一步的研究将集中于对相关犀牛Equi的肺部宿主反应，这是一种细菌，是免疫强化（AIDS）患者的机会性肺疾病的重要来源，也是造成经济损失和发病率作为幼马疾病的重要原因。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疗法开放新的研究途径。 公共卫生相关性：结核病是由于单一传染病毒剂而导致的主要死亡原因之一，并感染了世界人群的约1/3。相关的Rhodococcus Equi是艾滋病患者的机会感染，是马产业的经济损失 /发病率的原因。我们的项目将定义这些细菌与肺部免疫系统的初始相互作用，并生成新颖的免疫疗法方法。