Exercise-induced immunomodulation in the aged

老年人运动诱导的免疫调节

基本信息

批准号：
7408516
负责人：
Marian L Kohut
金额：
$ 48.72万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-15 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7408516
关键词：
A Mouse Adult Affect Age Alveolar Macrophages Animals Anti-Inflammatory Agents Anti-inflammatory Antibodies Antioxidants Antiviral Agents Appearance CD8-Positive T-Lymphocytes Cell Survival Cells Cessation of life Chronic Disease Clinical Collection Communicable Diseases Data Dendritic Cells Disease Elderly Equilibrium Exercise Exhibits Exposure to Gene Expression Genes Goals Immune Immune response Immune system Immunity Immunocompetence Immunology Impairment In Vitro Inbred BALB C Mice Infection Inflammation Inflammatory Influenza Interferon Type I Interferon-alpha Interleukin-10 Intervention Kinetics Lead Life Style Lung MHC Class II Genes Mediating Mediator of activation protein Moderate Exercise Molecular Molecular Biology Mus Organism Pathology Pathway interactions Pattern Phase Physiological Population Predisposition Production Proteins Range Rate Research Research Personnel Resolution Role STAT1 gene STAT4 gene Severities Shapes Signal Pathway Signal Transduction Signaling Molecule Stress System TLR7 gene Techniques Testing Therapeutic Tissues Toll-like receptors Training Viral Virus Virus Diseases Week Whole Organism Work age related aged base cell type chemokine concept cytokine emergency service responder human TLR7 protein immune function immunopathology immunoregulation immunosenescence improved in vivo influenzavirus innovation insight interdisciplinary approach lymph nodes macrophage member microbial mouse model programs research study response stressor theories virology

项目摘要

DESCRIPTION (provided by applicant): A significant decrease in immune responsiveness occurs with advancing age. The clinical consequences of immunosenescence include an increased susceptibility to and/or severity of infectious disease. Several intervention strategies have been proposed to restore immune function. One of the least well-studied approaches to improve immune response is physical exercise. The long term research objectives of our research group are to elucidate the mechanisms underlying the adaptations induced by moderate exercise that enhance immune responsiveness to infectious disease in aged populations. In this application, one goal is to determine the mechanistic adaptations induced by exercise that affect the initial pathways involved in recognition of viral infection that result in enhanced IFNalpha production. A second goal is to identify which of the pathways that can be triggered by IFNalpha lead to improved viral clearance and reduced immunopathology. The specific aims are: 1) Identify the mechanism(s) by which exercise training of aged animals increases IFNalpha production after influenza virus challenge, 2) Determine the extent to which the exercise-induced increase in IFNalpha regulates responses of dendritic cells and CD8+cells, 3) Identify the pathways involved in the response to IFNalpha that are altered by exercise, and 4) Further define the impact of exercise by determining the balance between pro-inflammatory / anti-inflammatory cytokines within the lungs and the subsequent effect on immunopathologically-mediated tissue damage, identify the cells producing these cytokines, and establish the role of IFNalpha as a mediator of these effects. A mouse model of influenza viral infection will be used. Aged BALB/c mice will be assigned to a moderate exercise group for 10 weeks or a non-exercise group. After exercise training, some experiments will involve an in vivo viral challenge to examine immune responses that occur in the intact animals, whereas other experiments will involve the collection of cells from mice after exercise training, and exposure to viral challenge in vitro. Different techniques will be used to identify the type of cells responding to challenge as well as the multiple pathways involved. Upon completion of these studies, we expect to indentify the exercise-induced adaptations involved in cellular defense against viral infection that subsequently shape the evolving immune response resulting in improved viral clearance and reduced immunopathology.

描述（由申请人提供）：随着年龄的增长，免疫反应能力显着下降。免疫衰老的临床后果包括感染性疾病的易感性和/或严重性增加。已经提出了几种干预策略来恢复免疫功能。体育锻炼是研究最少的改善免疫反应的方法之一。我们研究小组的长期研究目标是阐明适度运动引起的适应机制，增强老年人群对传染病的免疫反应。在此应用中，一个目标是确定运动引起的机械适应，这些适应会影响识别病毒感染的初始途径，从而导致 IFNα 产生增强。第二个目标是确定 IFNα 可以触发哪些途径来改善病毒清除并减少免疫病理。具体目标是：1) 确定老年动物运动训练在流感病毒攻击后增加 IFNα 产生的机制，2) 确定运动诱导的 IFNα 增加在多大程度上调节树突状细胞和 CD8+ 的反应细胞，3) 确定参与运动改变的 IFNα 反应的途径，以及 4) 通过确定肺部促炎/抗炎细胞因子之间的平衡以及随后对身体的影响，进一步确定运动的影响。免疫病理学介导的组织损伤，识别产生这些细胞因子的细胞，并确定 IFNα 作为这些效应介质的作用。将使用流感病毒感染的小鼠模型。老年 BALB/c 小鼠将被分配到 10 周的中等运动组或非运动组。运动训练后，一些实验将涉及体内病毒攻击，以检查完整动物中发生的免疫反应，而其他实验将涉及运动训练后从小鼠身上收集细胞，并在体外暴露于病毒攻击。将使用不同的技术来识别响应挑战的细胞类型以及涉及的多种途径。完成这些研究后，我们希望能够确定运动引起的适应，这些适应涉及细胞防御病毒感染的过程，从而形成不断发展的免疫反应，从而提高病毒清除率并减少免疫病理学。