Immune regulation to Coccidioides infection

对球孢子菌感染的免疫调节

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要球虫病或山谷热是由真菌球虫剂吸入引起的。健康影响山谷热感染的变化很大，对影响的生物学因素知之甚少感染后症状和健康并发症的严重程度。山谷热诊断，由于缺乏对宿主的基本免疫知识，治疗和疫苗的开发受到了阻碍对球虫剂的反应。我们小组的发布数据确定患者无法解决球球菌的感染可能是调节性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疾病的预后。该建议旨在定义调节性T细胞在控制对球虫下感染的反应中的机械作用以及免疫真菌控制中的抑制受体。这项研究的总体目标是提供基本关于对山谷热的免疫反应的知识，填补了知识的空白，作为改善的基础诊断，治疗和疫苗发育，以快速扩大真菌疾病。为了实现这一目标，我们将定义T细胞调节，动力学和在感染过程中定位的机制，并操纵使用免疫调节小鼠感染模型中的抗体调节和效应T细胞。虽然细节仍然不清楚，长期以来，细胞免疫反应对于有效免疫至关重要给球菌感染。在某些患者中，山谷热导致严重或长期临床疾病戏剧性的健康影响，包括慢性肺结节和肺部外传播。这提案将评估免疫调节如何调节球球菌感染期间的真菌清除率。