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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）是一种高毒性的中枢神经系统（CNS）人类病原体，是美国流行性脑炎的最常见原因。目前还没有疫苗或特定的抗病毒治疗方法为西尼罗河病毒，实现这一目标需要更全面地了解其发病机制。在CNS中，骨髓细胞，包括浸润性炎性单核细胞、巨噬细胞和活化的小胶质细胞，构成了对WNV脑炎的大部分细胞应答。目前，每个髓系亚群在调节病毒发病机制中的具体作用在很大程度上是未知的。本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的单核细胞的迁移和功能，3）表征在WNV脑炎期间表达CX3CR1的小胶质细胞的神经致病作用。详细了解骨髓细胞亚群的具体作用将提供深入了解其基本生物学及其对宿主防御的贡献。此外，我们的研究结果将提供新的干预策略的基础上，针对中枢神经系统中的骨髓细胞亚群，当需要有效的治疗是最关键的。