Identification of Pathways and Targets in Post-influenza Invasive Pulmonary Aspergillosis

流感后侵袭性肺曲霉病的途径和靶标的确定

基本信息

批准号：
10063634
负责人：
Keven Mara Robinson
金额：
$ 6.81万
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：
2020-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063634
关键词：
Affect Allergic Bronchopulmonary Aspergillosis Antiviral Agents Architecture Aspergillosis Aspergillus Aspergillus fumigatus Bacterial Pneumonia Cell physiology Cells Cellular Assay Cessation of life Clinical Critical Illness DNA Sequencing Facility Data Development Disease Future Genes Genomics Goals Health Hematopoietic Stem Cell Transplantation Heterogeneity Host Defense Human Immune Immune Targeting Immune response Immune system Immunocompromised Host Individual Infection Inflammation Influenza Influenza A virus Inhalation Inherited Interferons Invaded Investigation Knowledge Laboratories Learning Leukocytes Life Lung Lung Transplantation Lung infections Maps Methods Modeling Molecular Morbidity - disease rate Mus Mycoses Neutropenia PTPRC gene Pathway interactions Patients Play Population Predisposition Preparation Regulator Genes Reproduction spores Research Research Project Grants Research Support Resolution Respiratory System Respiratory Tract Infections Risk Risk Factors Sampling Secondary to Signal Pathway Signal Transduction Structure of parenchyma of lung Therapeutic Intervention Universities acquired immunodeficiency base cell type experience experimental study fungus inflammatory milieu influenza epidemic mortality mouse model novel therapeutic intervention pathogenic fungus prevent respiratory response single cell sequencing single-cell RNA sequencing superinfection transcriptome transcriptomics

项目摘要

PROJECT SUMMARY Fungal pathogens are a serious threat to human health. Invasive pulmonary aspergillosis (IPA) is a severe, life- threatening disease that occurs when Aspergillus fumigatus (AF) spores are inhaled into the respiratory tract and invade airway or lung tissue. More than 200,000 cases of invasive aspergillosis occur each year. A newly identified risk factor for IPA in critically ill patients is influenza infection. Influenza is a common respiratory illness that affects 5-20% of the population each year. Our long-term goal is to develop novel therapeutic interventions for use in clinical settings to prevent morbidity and mortality from IPA. The focus of this application is to identify cell signaling pathways that increase susceptibility to invasive fungal disease following influenza infection. We hypothesize that preceding influenza A infection inhibits leukocyte responses against secondary Aspergillus fumigatus infection through the induction of IFN, leading to invasive pulmonary aspergillosis. Our research aims include 1) To characterize the gene regulatory architecture of leukocytes at a single cell resolution during post- influenza invasive pulmonary aspergillosis. We will perform single cell RNA sequencing on CD45+ immune cells collected from lung tissue from (1) wild-type and (2) IFN -/- mice infected with aspergillus, influenza, and super- infected with influenza followed by aspergillus.

项目摘要真菌病原体是对人类健康的严重威胁。侵入性肺曲霉菌病（IPA）是一种严重的生活 - 当曲霉（AF）孢子遗传到呼吸道中时，发生威胁性疾病并入侵气道或肺组织。每年发生超过200,000例侵入性曲霉病。一个新的危重患者的IPA识别危险因素是影响力感染。流感是常见的呼吸道疾病每年影响5-20％的人口。我们的长期目标是开发新颖的治疗干预措施用于在临床环境中使用以防止IPA发病和死亡率。该应用程序的重点是确定影响力感染后增加对浸润性真菌疾病的敏感性的细胞信号通路。我们假设前面的影响影响白细胞反应对第二曲曲霉的反应通过诱导IFN感染富玛曲子，导致浸润性肺曲霉病。我们的研究目的包括1）表征白细胞在单个细胞分辨率下的基因调节结构影响肺曲霉病。我们将在CD45+免疫细胞上执行单细胞RNA测序从（1）野生型和（2）IFN-/ - 小鼠从肺组织中收集，感染了曲霉，有影响力和超级感染了影响力，然后是曲霉。