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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.

项目总结