Dectin-IL-17 axis, candidemia, and aging

Dectin-IL-17 轴、念珠菌血症和衰老

• 批准号: 8324518
• 负责人: DAVID VAN DUIN
• 金额: $ 7.85万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8324518
• 关键词: Age; Aging; Antifungal Agents; Antigen-Presenting Cells; Antigens; Biological Assay; Blood; C-Type Lectins; Candida; Candida albicans; Cell physiology; Cells; Chemotaxis; Clinic; Clinical; Clinical Research; Clinical Sciences; Data; Dendritic Cells; Deterioration; Disease; Elderly; Enrollment; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Future; Helper-Inducer T-Lymphocyte; Hospitals; Human; Immune System Diseases; Immune response; Immune system; Immunity; Infection; Interleukin-17; Intervention; Lead; Measures; Membrane Proteins; Methods; Mitogens; Modeling; Mus; Mycobacterium Infections; Mycoses; Outcome; Pathway interactions; Patients; Pattern recognition receptor; Phenotype; Physiological; Play; Proteins; RNA; Regulation; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; SYK gene; Sepsis; Serum; Signal Transduction; Stimulus; Stream; Surface; T cell differentiation; T memory cell; T-Cell Receptor; T-Lymphocyte; Testing; Translational Research; Vaccination; Western Blotting; adverse outcome; age effect; age group; age related; aged; animal data; base; candidemia; clinically relevant; dectin 1; immunosenescence; improved; monocyte; mortality; mouse dectin-2; mycobacterial; pathogen; peripheral blood; protein expression; response; tertiary care; therapeutic target

DESCRIPTION (provided by applicant): Older adults are more susceptible to severe infections and age is the single strongest predictor of mortality in Candida blood stream infections. Th17 T cells are a recently described important subset of effector T cells that produce IL-17 and have been implicated in antifungal and anti-mycobacterial immunity, as well as several auto-immune disorders. Signaling through the Dectin pathway on antigen-presenting cells promotes differentiation of specific T cells to the Th17 functional phenotype. Our preliminary data, as well as animal data suggest a dysregulation of Th17 T cells in human aging leading us to propose the hypothesis that human aging is associated with changes in the Dectin-IL-17 axis resulting in suboptimal immune responses and adverse outcomes in candidemia in older adults. This hypothesis will be tested by studying human age-related changes in the dectin-Th17 axis and determining whether Dectin expression or function is decreased and contributes to dysregulation of Th17 responses in older adults. In addition, we will extensively describe the induction of phenotype of Th17 T cells derived from older adults. We anticipate that these studies will lead to an improved understanding of regulation of immune responses in older adults, and may help to identify older adults at increased risk for adverse outcomes after candidemia.

描述（由申请人提供）：老年人更容易受到严重感染，年龄是念珠菌血流感染死亡率的单一最强预测因素。Th 17 T细胞是最近描述的产生IL-17的效应T细胞的重要子集，并且已经涉及抗真菌和抗分枝杆菌免疫以及几种自身免疫疾病。通过抗原呈递细胞上的Dectin途径的信号传导促进特异性T细胞分化为Th 17功能表型。我们的初步数据以及动物数据表明，人类衰老中Th 17 T细胞的失调导致我们提出这样的假设，即人类衰老与Dectin-IL-17轴的变化相关，导致老年人中念珠菌血症的次优免疫应答和不良结果。这一假设将通过研究人类年龄相关的dectin-Th 17轴的变化来检验，并确定Dectin表达或功能是否降低，是否有助于老年人Th 17反应的失调。此外，我们将广泛地描述来自老年人的Th 17 T细胞表型的诱导。我们预计，这些研究将有助于更好地了解老年人免疫反应的调节，并可能有助于识别念珠菌血症后不良结局风险增加的老年人。