Chemokine regulation of myeloid cell populations during West Nile virus infection

西尼罗河病毒感染期间骨髓细胞群的趋化因子调节

基本信息

批准号：
8903793
负责人：
Jean Kyou Lim
金额：
$ 35.26万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-05 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8903793
关键词：
Acute Address Antiviral Agents Antiviral Therapy Arbovirus Encephalitis Biological Process Biology Blood CCL2 gene CCL7 gene CX3CL1 gene Cells Cellular biology Coculture Techniques Data Development Future Goals Health Host Defense Human Immigration Immune response Infection Inflammatory Inflammatory Infiltrate Intervention Knowledge Lead Ligands Mediating Mediator of activation protein Microglia Monocytosis Mus Myelogenous Myeloid Cells Nature Neuraxis Neurons Outcome Pathogenesis Plasma Population Predisposition Production Regulation Reporter Role Source System Testing Therapeutic Transgenic Organisms United States Vaccines Viral Viral Pathogenesis Virulent Virus Diseases West Nile Encephalitis West Nile virus base chemokine chemokine receptor cohort effective therapy efficacy testing in vivo insight macrophage migration monocyte neurotropic new therapeutic target novel pathogen receptor response trafficking

项目摘要

DESCRIPTION (provided by applicant): West Nile virus (WNV) is a highly virulent human pathogen of the central nervous system (CNS) and the most common cause of epidemic encephalitis in the United States. There are no vaccines or specific antiviral treatments available for WNV, and accomplishing this requires a more complete understanding of its pathogenesis. In the CNS, myeloid cells, including infiltrating inflammatory monocytes, macrophages, and activated microglia, comprise the majority of the cellular response to WNV encephalitis. Currently, the specific role of each myeloid subset in regulating viral pathogenesis is largely unknown. The primary goal of this proposal is to understand the fundamental biology of myeloid cell populations during WNV infection. To do this, we will 1) establish the mechanisms and significance of WNV-induced monocyte mobilization, 2) define the migration and function of CCR2-expressing monocytes in the WNV-infected CNS, and 3) characterize the neuropathogenic role of CX3CR1-expressing microglia during WNV encephalitis. Detailed knowledge of the specific roles of myeloid cell subsets will provide insights into their fundamental biology and their contribution to host defense. Furthermore, our results will provide the basis for novel intervention strategies targeting myeloid cell subsets in the CNS, when the need for effective treatments is most critical.

描述（由申请人提供）：西尼罗河病毒（WNV）是一种对中枢神经系统（CNS）具有高毒力的人类病原体，也是美国流行性脑炎的最常见原因。没有可用的疫苗或特定的抗病毒治疗方法对于西尼罗河病毒来说，实现这一目标需要对其发病机制有更全面的了解。在中枢神经系统中，骨髓细胞，包括浸润性炎症单核细胞、巨噬细胞和活化的小胶质细胞，构成了对西尼罗河病毒脑炎的大部分细胞反应。目前，每个骨髓亚群在调节病毒发病机制中的具体作用尚不清楚。该提案的主要目标是了解西尼罗河病毒感染期间骨髓细胞群的基本生物学。为此，我们将 1) 建立 WNV 诱导的单核细胞动员的机制和意义，2) 定义 WNV 感染的 CNS 中表达 CCR2 的单核细胞的迁移和功能，以及 3) 表征表达 CX3CR1 的神经病理作用西尼罗河病毒脑炎期间的小胶质细胞。对骨髓细胞亚群具体作用的详细了解将有助于深入了解其基本生物学及其对宿主防御的贡献。此外，当最需要有效的治疗时，我们的结果将为针对中枢神经系统中的骨髓细胞亚群的新型干预策略提供基础。