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：
8760176
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/8760176
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 Encephalitis Future Goals 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 virus base chemokine chemokine receptor cohort effective therapy efficacy testing in vivo insight macrophage migration monocyte neurotropic new therapeutic target novel pathogen public health relevance 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）是中枢神经系统（CNS）的高度毒性人类病原体，是美国流行性脑炎最常见的原因。没有可用的疫苗或特定抗病毒治疗对于WNV，并完成此操作需要对其发病机理有更完整的了解。在中枢神经系统中，髓样细胞，包括浸润性炎症单核细胞，巨噬细胞和活化的小胶质细胞，包括大多数对WNV脑炎的细胞反应。当前，每个髓样子群在调节病毒发病机理中的特定作用在很大程度上尚不清楚。该提案的主要目的是了解WNV感染期间髓样细胞群体的基本生物学。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）定义在WNV感染的CNS中表达CCR2表达单核细胞的迁移和功能，以及3）表征WNV Enscephality wnv encephality的CX3CR1表达微胶质的神经疾病作用。详细了解髓样细胞子集的特定作用将为他们的基本生物学及其对宿主防御的贡献提供见解。此外，当对有效治疗的需求是最关键时，我们的结果将为针对CNS中髓样细胞亚群的新干预策略提供基础。