Interrogating inflammatory responses to SARS-CoV-2 infection in vivo

探究体内 SARS-CoV-2 感染的炎症反应

基本信息

批准号：
10692247
负责人：
Katrin Mayer-Barber
金额：
$ 15.14万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10692247
关键词：
2019-nCoV ACE2 Acute Respiratory Distress Syndrome Animals Blood Blood specimen COVID-19 COVID-19 patient Cell Death Cells Cessation of life Chemicals Complex Containment DNA Deoxyribonucleases Disease Disease Outcome Environment Epithelial Cells Etiology Functional disorder Genes Human Immune Immune response Individual Infection Inflammatory Inflammatory Response Innate Immune Response Interleukin-1 Interleukin-18 Interleukin-6 Lactate Dehydrogenase Lead Lung Lytic Modality Molecular Mus Mycobacterium tuberculosis Myeloid Cells Natural Immunity Necrosis Outcome Pathogenesis Pathology Pathway interactions Patients Pattern Pneumonia Pulmonary Pathology Recombinants Reporting Research Role SARS coronavirus SARS-CoV-2 immunity SARS-CoV-2 infection Severe Acute Respiratory Syndrome Signal Transduction Techniques Tissues Transgenic Organisms Tuberculosis Viral Virus Virus Diseases airway epithelium antiviral immunity biosafety level 3 facility coronavirus disease cytokine cytokine release syndrome eosinophil extracellular in vivo in vivo Model inhibitor migration mouse model neutralizing antibody neutrophil neutrophil elastase inhibitor operation prevent severe COVID-19 tool

项目摘要

The lungs of patients suffering from severe Coronavirus Disease 2019 (COVID-19) present with pneumonia and significant tissue damage which can lead to acute respiratory distress syndrome (ARDS) and death. This tissue destruction is caused not only by the etiological, cytopathic Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) itself, but also a dysregulated host immune response. A phenomenon termed cytokine storm", which is characterized by high levels of pro-inflammatory cytokines such as IL-6 and IL-1, has been observed as a consequence of this dysregulated antiviral immunity. Understanding the complex host response to SARS-CoV-2 infection is a crucial global challenge. We leverage here our current expertise in inflammatory cytokines and pulmonary pathophysiology, operation in our high-containment (BSL3) research environment and importantly, animal BSL3 facilities, to investigate the host molecular and cellular mechanisms that contribute to pathogenesis during SARS-CoV-2 infection. In particular, we will focus on the very earliest innate immune responses to to viral infection in the lung, with emphasis on tissue-resident myeloid cell subsets and lung epithelial cells.

患有严重 2019 年冠状病毒病 (COVID-19) 的患者肺部会出现肺炎和严重的组织损伤，可能导致急性呼吸窘迫综合征 (ARDS) 和死亡。这种组织破坏不仅是由病因学、细胞病变的严重急性呼吸综合征-冠状病毒-2 (SARS-CoV-2) 本身引起的，也是宿主免疫反应失调引起的。一种被称为“细胞因子风暴”的现象，其特征是高水平的促炎细胞因子，如 IL-6 和 IL-1，已被观察到是这种抗病毒免疫失调的结果。了解宿主对 SARS-CoV 的复杂反应2 感染是一个关键的全球挑战，我们利用我们目前在炎症细胞因子和肺部病理生理学方面的专业知识、在我们的高密闭 (BSL3) 研究环境以及重要的动物 BSL3 设施中的操作，来研究导致 2 感染的宿主分子和细胞机制。特别是，我们将重点关注肺部对病毒感染的最早的先天免疫反应，重点关注组织驻留的骨髓细胞亚群和肺上皮细胞。