Exercise-induced immunomodulation in the aged: Mechanisms

老年人运动引起的免疫调节：机制

基本信息

批准号：
7778304
负责人：
Marian L Kohut
金额：
$ 49.29万
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/7778304
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 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 Regulatory T-Lymphocyte 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 Whole Organism Work age related aged base cell type chemokine cytokine emergency service responder human TLR7 protein immune function immunopathology immunoregulation immunosenescence improved in vivo influenzavirus innovation insight interdisciplinary approach lifestyle factors 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，免疫反应能力显着降低。免疫衰老的临床后果包括对传染病的敏感性增加和/或严重性。已经提出了几种干预策略来恢复免疫功能。改善免疫反应的最不足的方法之一是体育锻炼。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的机制，从而增强了老年人群中对感染性疾病的免疫反应能力。在此应用中，一个目标是确定锻炼引起的机械适应，该运动影响识别病毒感染所涉及的初始途径，从而增强了IFNALPHA的产生。第二个目标是确定IFNALPHA可以触发的哪些途径可改善病毒清除率并减少免疫病理学。具体目的是：1）确定衰老动物运动训练在流感病毒挑战后增加IFNALPHA的产生的机制，2）确定运动诱导的IFNALPHA运动的增加的程度，调节了树突状细胞和CD8+细胞的反应，CD8+细胞的响应是通过对IFNALPH的响应进行了涉及的措施，并确定了锻炼的措施，并通过锻炼的措施进行了进一步的影响，并在IFNALPHA中的响应范围进行了影响。肺内的抗炎细胞因子以及随后对免疫病理学介导的组织损伤的影响，鉴定产生这些细胞因子的细胞，并确定Ifnalpha作为这些作用的介体的作用。将使用流感病毒感染的小鼠模型。老年BALB/C小鼠将分配到一个适度的运动组10周或非运动组。锻炼训练后，一些实验将涉及一个体内病毒挑战，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小鼠的细胞收集，并在体外暴露于病毒挑战。不同的技术将用于确定响应挑战的细胞类型以及所涉及的多个途径。这些研究完成后，我们期望将运动诱导的针对病毒感染的运动诱导的适应性降低，随后塑造了不断发展的免疫反应，从而改善了病毒清除率并减少了免疫病理学。