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Pulmonary gamma-delta T cells in lung infection

肺部感染中的肺 γ-δ T 细胞

基本信息

批准号：
10424454
负责人：
Shelton Wiley Wright
金额：
$ 16.08万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10424454
关键词：
Address Aerosols Animal Model Applications Grants Bacteria Bacterial Vaccines Blood donor Burkholderia Burkholderia pseudomallei Cells Cessation of life Characteristics Childhood Complement Containment Critical Illness Data Development Development Plans Disease Disease model Fatality rate Fc Receptor Foundations Gene Expression Genes Goals Health Hospitalization Host Defense Host resistance Human Immune response Immune system Immunology Immunotherapy Impairment Infection Inflammation Inflammatory Inflammatory Response Intensive Care Interferon Type II Interleukin-17 K-Series Research Career Programs Leukocytes Lower Respiratory Tract Infection Lung Lung infections Lymphocyte Melioidosis Mentors Mentorship Methods Modeling Mucous Membrane Mus Neutrophil Infiltration Patient Recruitments Patients Peripheral Phenotype Physicians Play Pneumonia Positioning Attribute Process Prospective Studies Pulmonary Inflammation Receptor Cell Research Research Personnel Research Project Grants Role Scientist Soil T cell response T-Cell Activation T-Cell Receptor T-Lymphocyte Subsets Testing Therapeutic Tissues Training Training Programs Training and Infrastructure United States Universities Washington base bioweapon career development cohort community acquired pneumonia cytokine differential expression human model immunomodulatory therapies improved in vivo innovation insight knockout animal mouse model multidisciplinary neutrophil novel pathogen peripheral blood pneumonia model programs single-cell RNA sequencing transcriptomics translational approach translational physician translational research program translational scientist γδ T cells

项目摘要

PROJECT SUMMARY Lower respiratory tract infections, including pneumonia, are the most common cause of infection-related death worldwide. γδ T cells are highly conserved leukocytes possessing innate-like immune response characteristics. Enriched in the mucosa, γδ T cells may play an outsized role in regulating pulmonary inflammatory responses and have been proposed as a basis for novel immunotherapies. However, data concerning the inflammatory role of pulmonary γδ T cells during pneumonia in humans are limited. Dr. Shelton Wright is a pediatric intensive care physician-scientist whose goal is to obtain the necessary training to become an independent translational investigator of pulmonary host defense. He has established a translational research program that has identified a critical role of γδ T cells in pulmonary melioidosis, a highly lethal cause of pneumonia. Based on these findings, he has developed a central hypothesis that host resistance to pulmonary melioidosis is dependent on an IL-17+ γδ T cell inflammatory response. Dr. Wright's research goal is to determine the mechanisms underlying the host γδ T cell inflammatory response during severe lung infection. Using pulmonary melioidosis as a model for severe lung infection, Dr. Wright will test his hypothesis through the following 3 Aims: 1) Determine the role of γδ T cells in lung inflammation during pulmonary melioidosis in vivo; 2) Identify differential human γδ T cell inflammatory responses to B. pseudomallei infection in the ex-vivo lung compared to peripheral blood; and 3) Characterize γδ T cell activation in patients with early pulmonary melioidosis. The Career Development Plan for this grant proposal will provide Dr. Wright with critical training in pulmonary immunology, transcriptomics and high containment pathogen research. Dr. Wright has leveraged the outstanding training infrastructure at the University of Washington and its affiliates to bring together a wide array of experts in these fields to provide targeted mentorship for this proposal. Dr. Wright's multidisciplinary team of mentors will greatly complement his proposed research project along with a carefully selected didactic program. The data generated by his proposal and the skillsets developed from his training program will significantly facilitate Dr. Wright's goal of developing into an independent translational physician-scientist investigating the mechanisms of pulmonary host defense during severe lung infection.

项目总结