CD40 regulation of acute virus infection

CD40对急性病毒感染的调节

基本信息

批准号：
9893167
负责人：
Wendy Jean Maury
金额：
$ 25.97万
依托单位：
UNIVERSITY OF IOWA
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：
2020-03-11 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9893167
关键词：
Acute Address Adoptive Transfer Antiviral Agents Antiviral Response Cell membrane Cells Cessation of life Characteristics Dendritic Cells Development Disease Outbreaks Ebola virus Ebola virus envelope glycoprotein Endothelial Cells Environment Epithelial Cells Event Fibroblasts Filoviridae Infections Filovirus Genes Glycoproteins IFNGR1 gene IL12RB1 gene Immune Immune response Infection Infection Control Innate Immune Response Interferon Type II Interferons Interleukin-12 JUN gene Knowledge Lead Ligation Maintenance Mediating Modeling Morbidity - disease rate Mus Myelogenous Natural Immunity Pathogenesis Pathway interactions Peritoneal Peritoneal Macrophages Peritoneum Population Production Public Health Receptor Signaling Recombinants Regulation Role Signal Pathway Signal Transduction Specificity Stomatitis TNFRSF5 gene TNFSF5 gene TRAF6 gene Testing Therapeutic Intervention Time Tissues Vaccines Viral Pathogenesis Viral load measurement Viremia Virus Virus Diseases Virus Replication adaptive immunity cell type cytokine immunoregulation in vivo innate immune pathways intraperitoneal macrophage mortality new therapeutic target receptor recruit

项目摘要

CD40 signaling is well established to enhance development and maintenance of adaptive immunity. However, the role of CD40 signaling during innate immune responses is more poorly studied and an important role for CD40 signaling in rapid control of acute virus infections is not currently appreciated. Here, we provide strong preliminary findings that CD40 signaling is critical for early stimulation of innate immune pathways in peritoneal macrophages, resulting in control of acute viral infection. In these proposed studies, we will use both Ebola virus (EBOV) and a BSL2 model virus of EBOV to identify the CD40+ cellular compartment(s) required for protection and understand the breadth of cell populations that use CD40 signaling to control EBOV infection. Elucidation of these cell populations will elucidate targeted approaches that can lead to therapeutic interventions.

CD40信号已建立，以增强自适应免疫的发育和维持。然而，目前尚不理解CD40信号在先天免疫反应中的作用，而CD40信号在快速控制急性病毒感染中的重要作用却是不受欢迎的。在这里，我们提供了有力的初步发现，即CD40信号对于早期刺激腹膜巨噬细胞中先天免疫途径至关重要，从而控制了急性病毒感染。在这些拟议的研究中，我们将同时使用EBOV的埃博拉病毒（EBOV）和BSL2模型病毒来识别保护的CD40+细胞隔室，并了解使用CD40信号传导控制EBOV感染的细胞群体的广度。阐明这些细胞群体将阐明可能导致治疗干预措施的目标方法。