Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection

IL-17RA 在控制肺炎克雷伯菌肺部感染中的域特异性作用

基本信息

批准号：
10063356
负责人：
Giraldina Trevejo-Nunez
金额：
$ 7.83万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-20 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063356
关键词：
Accounting Address Alveolar Cell Animal Model Biological Response Modifiers Cells Clinical Communities Disease Distal Endothelial Cells Epithelial Epithelial Cells Epithelium Event Fibroblasts Genes Genetic study Goals Histidine Immune Immune response Immunity Immunocompromised Host Immunologics Impairment In Vitro Infection Infection Control Inflammation Interleukin-17 Klebsiella pneumoniae Knowledge Laboratories Length Lung Lung infections Mediating Mediator of activation protein Medical Messenger RNA Molecular Morbidity - disease rate Multi-Drug Resistance Mus Mutant Strains Mice NF-kappa B Pneumonia Positioning Attribute Predisposition Process Proteins Receptor Signaling Research Resistance Resistance profile Resolution Role Secondary to Signal Transduction Stromal Cells Testing United States bronchial epithelium cell type cytokine experimental study healthcare-associated infections in vivo insight interleukin-17C interleukin-17E mortality mouse model mutant pathogen receptor receptor function response single-cell RNA sequencing transcriptome sequencing

项目摘要

ABSTRACT IL-17 is an essential mediator of immunity to Klebsiella pneumoniae (KP). Animal models lacking IL-17 signaling or having IL-17 receptor (IL-17R) deficiency are susceptible to KP pneumonia. Although considerable research effort has focused on how Th17 cells are generated and regulated, the mechanisms by which IL-17 and its receptor IL-17R mediate specific downstream signals in relevant disease processes such as KP pneumonia are not fully elucidated. Our efforts to understand KP pneumonia in mouse models revealed that the distal domain of IL-17RA, also known as CBAD, is indispensable to control this infection. Thus, we propose to determine the immune and molecular mechanisms by which the IL-17RA CBAD domain constrains KP pneumonia. We will also perform parallel analyses to evaluate the cell-type-specific response by single-cell RNASeq. The findings generated from this proposal will help us understand IL-17- dependent signaling mechanism by which KP pneumonia can be controlled and to evaluate the lung immune response at a single cell resolution.

抽象的 IL-17 是肺炎克雷伯菌 (KP) 免疫的重要介质。缺乏 IL-17 信号传导的动物模型或有IL-17受体（IL-17R）缺陷者易患KP肺炎。尽管进行了大量研究工作重点是 Th17 细胞如何产生和调节、IL-17 及其作用机制受体 IL-17R 在 KP 肺炎等相关疾病过程中介导特定的下游信号没有完全阐明。我们在小鼠模型中了解 KP 肺炎的努力表明，远端区域 IL-17RA（也称为 CBAD）对于控制这种感染是必不可少的。因此，我们建议确定 IL-17RA CBAD 结构域限制 KP 肺炎的免疫和分子机制。我们将还进行并行分析以评估单细胞 RNASeq 的细胞类型特异性反应。研究结果该提案产生的结果将帮助我们理解 IL-17 依赖性信号传导机制，KP 通过该机制可以控制肺炎并以单细胞分辨率评估肺部免疫反应。