Immune regulation to Coccidioides infection

对球孢子菌感染的免疫调节

• 批准号: 10731031
• 负责人: Katrina K Hoyer
• 金额: $ 44.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731031
• 关键词: Activities of Daily Living; Antibodies; Biological Factors; California; Cell Count; Cell physiology; Cells; Chronic; Chronic Disease; Clinical; Coccidioides; Coccidioides immitis; Coccidioides posadasii; Coccidioidomycosis; Collaborations; Data; Diagnosis; Diagnostic; Disease; Disease Outcome; Disease susceptibility; Dust; Effectiveness; Foundations; Frequencies; Future; Gene Expression; Generations; Goals; Health; Image; Immune; Immune response; Immunity; Immunology; Immunotherapy; Impaired health; Impairment; Incidence; Infection; Infection Control; Inhalation; Kinetics; Knowledge; Laboratories; Link; Lung; Lung nodule; Measures; Modeling; Mus; Mycoses; Outcome; Patients; Phenotype; Predictive Factor; Predisposition; Process; Publishing; Rapid diagnostics; Regulatory T-Lymphocyte; Research; Resistance; Role; Severities; Southwestern United States; Symptoms; T cell differentiation; T cell regulation; T cell response; T-Lymphocyte; Therapeutic; Training; Vaccines; anergy; chronic infection; desert fever; effector T cell; exhaustion; experience; fungus; health care disparity; immunoregulation; improved; migration; novel; pathogen; pathogenic fungus; pediatric patients; prevent; programmed cell death protein 1; receptor; receptor expression; research study; response; targeted treatment; therapy development; vaccine development

PROJECT SUMMARY Coccidioidomycosis, or Valley fever, is caused by inhalation of the fungus Coccidioides. The health impacts of Valley fever infection vary dramatically, and little is known about the biological factors that influence the severity of symptoms and health complications experienced following infection. Valley fever diagnosis, treatment and vaccine development have been hampered by a lack of basic immune knowledge about the host response to Coccidioides. Published data from our group determined that the inability of patients 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. This proposal seeks to define the mechanistic role of regulatory T cells in controlling responses to Coccidioides infection and the influence of inhibitory receptors in immune fungal control. The overall goal of this research study is to provide fundamental knowledge about immune responses to Valley fever, filling gaps in knowledge, as a foundation to improve diagnosis, treatment and vaccine development for a rapidly expanding fungal disease. To achieve this goal, we will define the mechanisms of T cell regulation, kinetics and localization during infection, and manipulate regulatory and effector T cells using immune modulating antibodies in mouse infection models. Although the details are still unclear, cellular immune responses have long been shown to be critical for effective immunity to Coccidioides infection. In some patients, Valley fever results in a severe or prolonged clinical illness with dramatic health impacts, including chronic pulmonary nodules and dissemination outside the lungs. This proposal will evaluate how immune regulation modulates fungal clearance during Coccidioides infection.

项目概要 球孢子菌病或谷热是由吸入球孢子菌引起的。对健康的影响 谷热感染的发生率差异很大，但人们对影响谷热病的生物学因素知之甚少。 感染后出现的症状和健康并发症的严重程度。谷热诊断， 由于缺乏有关宿主的基本免疫知识，治疗和疫苗开发受到阻碍 对球孢子菌的反应。我们小组公布的数据表明，患者无法解决 球孢子菌感染可能是调节性 T 细胞频率和功能能力升高的结果，并且 调节性 T 细胞频率可以预测诊断时患者的疾病结果。该提案旨在定义 调节性T细胞在控制球孢子菌感染反应中的机制作用及其影响 免疫真菌控制中的抑制性受体。本研究的总体目标是提供基础 关于谷热免疫反应的知识，填补知识空白，作为改善的基础 针对迅速蔓延的真菌病的诊断、治疗和疫苗开发。为了实现这一目标，我们 将定义感染过程中 T 细胞调节、动力学和定位的机制，并操纵 在小鼠感染模型中使用免疫调节抗体的调节性和效应性 T 细胞。虽然 细节仍不清楚，细胞免疫反应早已被证明对于有效免疫至关重要 球孢子菌感染。在一些患者中，山谷热会导致严重或长期的临床疾病 严重的健康影响，包括慢性肺结节和肺外传播。这 该提案将评估球孢子菌感染期间免疫调节如何调节真菌清除。