Exercise-induced immunomodulation in the aged

老年人运动诱导的免疫调节

• 批准号: 7614466
• 负责人: Marian L Kohut
• 金额: $ 48.55万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 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/7614466
• 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; 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

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，免疫反应性显著下降。免疫衰老的临床后果包括增加对传染病的易感性和/或严重程度。已经提出了几种干预策略来恢复免疫功能。在改善免疫反应的方法中，研究得最少的是体育锻炼。我们研究小组的长期研究目标是阐明适度运动诱导的适应机制，增强老年人对传染病的免疫反应。在这个应用中，一个目标是确定运动诱导的机制适应，影响病毒感染识别的初始途径，从而导致ifn - α的产生增强。第二个目标是确定哪些途径可以由IFNalpha触发，从而改善病毒清除和减少免疫病理。具体目标是：1)确定老年动物在流感病毒攻击后运动训练增加ifn - α产生的机制；2)确定运动诱导的ifn - α增加对树突状细胞和CD8+细胞反应的调节程度；3)确定运动改变的ifn - α反应所涉及的途径。4)通过确定肺内促炎/抗炎细胞因子之间的平衡以及随后对免疫病理介导的组织损伤的影响，进一步确定运动的影响，识别产生这些细胞因子的细胞，并确定ifna - α作为这些影响的中介的作用。将使用流感病毒感染的小鼠模型。老龄BALB/c小鼠分为中度运动组和非运动组，为期10周。运动训练后，一些实验将涉及体内病毒攻击，以检查发生在完整动物中的免疫反应，而其他实验将涉及运动训练后小鼠细胞的收集，并暴露于体外病毒攻击。将使用不同的技术来识别对挑战作出反应的细胞类型以及所涉及的多种途径。在完成这些研究后，我们期望确定运动诱导的适应参与细胞防御病毒感染，随后塑造进化的免疫反应，从而提高病毒清除和减少免疫病理。