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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信号传导被充分确立以增强适应性免疫的发展和维持。然而，CD40信号传导在先天性免疫应答中的作用研究得更少，并且CD40信号传导在快速控制急性病毒感染中的重要作用目前还没有被认识到。在这里，我们提供了强有力的初步发现，CD40信号传导是至关重要的先天免疫途径的早期刺激腹腔巨噬细胞，导致控制急性病毒感染。在这些拟议的研究中，我们将使用埃博拉病毒（EBOV）和EBOV的BSL 2模型病毒来鉴定保护所需的CD40+细胞区室，并了解使用CD40信号传导控制EBOV感染的细胞群的广度。这些细胞群的阐明将阐明可以导致治疗干预的靶向方法。