Regulatory T cell function in predicting Valley fever outcomes

项目总结 球孢子菌病，称为谷热，是由地方性的真菌病原体(球孢子菌)引起的。 位于加利福尼亚州、亚利桑那州、墨西哥北部和南美洲干旱地区的圣华金山谷。年的发病率 加利福尼亚州正在上升，有证据表明，这种疾病可以在非流行地区找到 包括华盛顿州。人口扩张、旅行、探测和/或天气变化似乎是 有助于扩大地方病流行区域。谷热感染对健康的影响可能在以下几个方面 从肤浅到致命。对于60%被感染但没有表现出山谷热症状的人来说， 这种疾病的影响可能微乎其微。对于40%的有症状的患者，大多数会出现症状 类似于流感，这种情况不需要治疗就会消失。然而，这些患者可能会经历 在很长一段时间内严重损害健康。对于1%的患者来说，山谷热会导致严重的 或长期临床疾病，严重影响健康，包括慢性肺结节或空洞， 有可能误诊，甚至死亡。疾病经常被误诊为细菌感染，通常 导致在做出正确诊断之前进行了几轮抗生素治疗。山谷对健康的影响 因此，发烧感染差异很大，对影响其严重程度的生物因素知之甚少。 感染后出现的症状和健康并发症。 尽管细节仍不清楚，但细胞免疫反应长期以来一直被证明是 对球虫感染的有效免疫力。我们最近确定不能分解球虫 感染可能是调节性T细胞频率和功能能力增加的结果，而调节性T细胞 细胞频率可以在诊断时预测患者的疾病结果。我们建议：1)定义表型和 球虫感染患者早期疾病中调节性T细胞的功能，2)确定一种 可用于诊断的生物标记物算法，用于校准这些患者的治疗攻击性 最有可能发展成慢性球孢子菌病。该项目的成功完成将为 诊断工具，用于在患者病程早期识别患者，以便进行更积极的治疗和更密切的联系 监测治疗后的复发，并将更好地确定慢性病背后的免疫机制 球孢子虫病。

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.