Regulatory T cell function in predicting Valley fever outcomes

调节性 T 细胞功能预测谷热结果

• 批准号: 9979119
• 负责人: Katrina K Hoyer
• 金额: $ 23.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-09 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979119
• 关键词: Activities of Daily Living; Acute; Adult; Aftercare; Age; Algorithms; Antibiotic Therapy; Antifungal Agents; Area; Arizona; Bacterial Infections; Biological Factors; Biological Markers; Blood; California; Case Study; Cell physiology; Cells; Cessation of life; Child; Childhood; Chronic; Chronic Disease; Clinic; Clinical; Coccidioides; Coccidioides immitis; Coccidioides posadasii; Coccidioidomycosis; Contracts; Data; Data Set; Detection; Diagnosis; Diagnostic; Disease; Disease Outcome; Dust; Evaluation; Frequencies; Health; Immune; Immune response; Immunity; Immunologic Factors; Immunologic Markers; Impaired health; Incidence; Infection; Inhalation; Knowledge; Lung nodule; Measurement; Methods; Mexico; Modeling; Monitor; Mus; Outcome; Patient Care; Patients; Pharmaceutical Preparations; Phenotype; Population; Predictive Factor; Recurrent disease; Regulatory T-Lymphocyte; Relapse; Resolution; Severities; Severity of illness; Soil; South America; Southwestern United States; Symptoms; Testing; Time; Translational Research; Travel; Vaccines; Washington; Weather; acute infection; adaptive immune response; aggressive therapy; base; chronic infection; desert fever; eosinophil; experience; flu; fungus; improved; neutrophil; novel; older patient; pathogenic fungus; pediatric patients; peripheral blood; prediction algorithm; predictive modeling; predictive test; prevent; research study; response; side effect; tool; transmission process

PROJECT SUMMARY Coccidioidomycosis, known as Valley fever, is caused by the fungal pathogen (Coccidioides) endemic to the San Joaquin Valley in California, Arizona, northern Mexico and arid areas of South America. Incidence in California is on the rise, and there is evidence indicating that the disease can be found in non-endemic regions including Washington State. Population expansion, travel, detection and/or weather changes appear to be contributing to an expanding endemic region. The health impacts of Valley fever infection can range from superficial to lethal. For the 60% of people who are infected, but do not display symptoms of Valley fever, the impact of the disease is likely to be minimal. For the 40% of symptomatic patients, most will display symptoms similar to the flu and the condition will resolve without treatment. Nevertheless, these patients can experience significantly impaired health for a lengthy period of time. For 1% of the patients, Valley fever results in a severe or prolonged clinical illness with dramatic health impacts, including chronic pulmonary nodules or cavities, with the potential for misdiagnosis, and even death. Disease is often misdiagnosed as a bacterial infection, often resulting in several rounds of antibiotic treatments before a correct diagnosis. The health impacts of Valley fever infection thus vary dramatically, and little is known about the biological factors that influence the severity of symptoms and health complications experienced following infection. Although the details are still unclear, cellular immune responses have long been shown to be critical for effective immunity to Coccidioides infection. We recently determined that the inability to resolve Coccidioides infection may be a result of elevated regulatory T cell frequency and functional capacity, and that regulatory T cell frequency may predict patient disease outcome at diagnosis. We propose to: 1) define the phenotype and function of regulatory T cells in Coccidioides infected patients during early disease, and 2) to define a biomarker algorithm that can be used at diagnosis for calibrating treatment aggressiveness for those patients most likely to develop chronic cocciodiomycosis. The successful completion of this project will provide diagnostic tools to identify patients earlier in their disease course for more aggressive treatment and closer monitoring for relapse after treatment, and will better define the immune mechanisms underlying chronic cocciodiomycosis.

项目摘要 球虫菌病被称为山谷热，是由真菌病原体（球虫剂）引起的 加利福尼亚，亚利桑那州，墨西哥北部和南美干旱地区的圣华金山谷。发病率 加利福尼亚正在上升，有证据表明该疾病可以在非流行地区发现 包括华盛顿州。人口扩展，旅行，检测和/或天气变化似乎是 促成不断扩大的地方性地区。山谷热感染的健康影响可能从 表面致死。对于60％的感染者，但不显示山谷热的症状， 该疾病的影响可能很小。对于40％的有症状患者，大多数会表现出症状 与流感类似，情况将在没有治疗的情况下解决。尽管如此，这些患者可以体验 长时间的健康状况大大受损。对于1％的患者，山谷发烧会导致严重 或长时间的临床疾病，具有巨大健康影响，包括慢性肺结节或空腔，具有 误诊甚至死亡的潜力。疾病通常被误诊为细菌感染，通常 在正确诊断之前，导致几轮抗生素治疗。山谷的健康影响 因此，发烧感染变化很大，对影响严重程度的生物学因素知之甚少 感染后经历的症状和健康并发症。 尽管细节仍不清楚，但长期以来一直证明细胞免疫反应至关重要 有效免疫对球虫细胞感染。我们最近确定无法解决球孢菌素 感染可能是调节性T细胞频率和功能能力升高的结果，该调节性T 细胞频率可以预测诊断时患者疾病的结果。我们建议：1）定义表型和 在早期疾病期间，球虫下感染患者的调节性T细胞的功能，以及2） 可用于诊断的生物标志物算法，用于为这些患者校准治疗侵略性 最有可能发展慢性肠球菌病。该项目的成功完成将提供 诊断工具可在疾病病程中早期识别患者，以进行更具侵略性的治疗和更接近 监测治疗后的复发，并将更好地定义慢性的免疫机制 Cocciodiomycisois。