Pulmonary gamma-delta T cells in lung infection

肺部感染中的肺 γ-δ T 细胞

• 批准号: 10623319
• 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
• 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/10623319
• 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; Gene Expression; Genes; Goals; Health; Hospitalization; Host Defense; Host resistance; Human; IL17 gene; Immune response; Immune system; Immunology; Immunotherapy; Impairment; Infection; Inflammation; Inflammatory; Inflammatory Response; Intensive Care; Interferon Type II; 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; 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; novel therapeutic intervention; pathogen; peripheral blood; pneumonia model; programs; single-cell RNA sequencing; skills; transcriptomics; translational approach; translational physician; translational research program; translational scientist; γδ T cells

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.

项目摘要 包括肺炎在内的下呼吸道感染是感染相关死亡的最常见原因 国际吧γδ T细胞是高度保守的白细胞，具有先天性免疫应答特征。 γδ T细胞在肺粘膜中富集，可能在调节肺部炎症反应中发挥重要作用 并且已经被提议作为新的免疫疗法的基础。然而，关于炎症的数据 肺γδ T细胞在人类肺炎中的作用有限。谢尔顿·赖特医生是儿科医生 重症监护医生，科学家，其目标是获得必要的培训，成为一个 肺宿主防御的独立翻译研究者。他建立了一个翻译 一个研究项目已经确定了γδ T细胞在肺类鼻疽中的关键作用， 肺炎。基于这些发现，他提出了一个中心假设，即宿主对 肺类鼻疽病依赖于IL-17+ γδ T细胞炎症反应。 博士Wright的研究目标是确定宿主γδ T细胞炎症反应的潜在机制 在严重肺部感染期间。使用肺类鼻疽作为严重肺部感染的模型，Wright博士将 通过以下3个目的来验证他的假设：1）确定γδ T细胞在肺炎症中的作用， 体内肺类鼻疽病; 2）鉴定对B的不同人γδ T细胞炎症反应。 与外周血相比，离体肺中的假鼻疽感染;以及3）表征γδ T细胞 早期肺类鼻疽患者的活化。 这项拨款提案的职业发展计划将为Wright博士提供肺外科方面的关键培训。 免疫学、转录组学和高遏制病原体研究。赖特博士利用了 优秀的培训基础设施在华盛顿大学及其附属机构，汇集了广泛的 这些领域的一系列专家为该提案提供有针对性的指导。赖特博士的多学科 导师团队将大大补充他提出的研究项目沿着与精心挑选的教学 程序.他的建议产生的数据和从他的培训计划中开发的技能将 大大促进了Wright博士发展成为一名独立翻译医生-科学家的目标 探讨严重肺部感染时肺部宿主防御机制。

项目成果

Enhanced bedside mortality prediction combining point-of-care lactate and the quick Sequential Organ Failure Assessment (qSOFA) score in patients hospitalised with suspected infection in southeast Asia: a cohort study.

• DOI: 10.1016/s2214-109x(22)00277-7
• 发表时间: 2022-09
• 期刊: LANCET GLOBAL HEALTH
• 影响因子: 34.3
• 作者: Wright, Shelton W.;Hantrakun, Viriya;Rudd, Kristina E.;Lau, Chuen-Yen;Lie, Khie Chen;Nguyen Van Vinh Chau;Teparrukkul, Prapit;West, T. Eoin;Limmathurotsakul, Direk
• 通讯作者: Limmathurotsakul, Direk

IL-1R2-based biomarker models predict melioidosis mortality independent of clinical data.

基于IL-1R2的生物标志物模型可预测与临床数据无关的黑胶病死亡率。

• DOI: 10.3389/fmed.2023.1211265
• 发表时间: 2023
• 期刊: Frontiers in medicine
• 影响因子: 3.9