Interferons in Neurobrucellosis

神经布鲁氏菌病中的干扰素

基本信息

批准号：
10722398
负责人：
Jerod Skyberg
金额：
$ 19.39万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722398
关键词：
Adoptive Transfer Animal Model Animals Anti-Bacterial Agents Brain Brucella Brucellosis Cells Central Nervous System Central Nervous System Infections Compensation Complement Complement Activation Complication Control Animal Data Defect Development Disease Gene Expression Profile Gene Expression Regulation Goals Human IFNAR1 gene IFNGR1 gene Immune Impairment In Vitro Infection Infection Control Inflammation Inflammatory Interferon Type I Interferon Type II Interferons Lymphoid Cell Macrophage Mediating Meningitis Microglia Modeling Mus Myelogenous Nervous System Physiology Neurologic Neurologic Dysfunctions Pathogenesis Pathology Pathway interactions Polysaccharides Predisposition Production Resistance Role STAT1 gene STAT2 gene Signal Pathway Signal Transduction T-Lymphocyte Testing Therapeutic Up-Regulation Zoonoses antimicrobial blood-brain barrier crossing blood-brain barrier permeabilization brain dysfunction cell type complement pathway mouse model neglect neuron apoptosis pathogenic bacteria protective effect response synaptic pruning transcription factor transcriptome sequencing type I interferon receptor

Adoptive Transfer Animal Model Animals Anti-Bacterial Agents Brain Brucella Brucellosis Cells Central Nervous System Central Nervous System Infections Compensation Complement Complement Activation Complication Control Animal Data Defect Development Disease Gene Expression Profile Gene Expression Regulation Goals Human IFNAR1 gene IFNGR1 gene Immune Impairment In Vitro Infection Infection Control Inflammation Inflammatory Interferon Type I Interferon Type II Interferons Lymphoid Cell Macrophage Mediating Meningitis Microglia Modeling Mus Myelogenous Nervous System Physiology Neurologic Neurologic Dysfunctions Pathogenesis Pathology Pathway interactions Polysaccharides Predisposition Production Resistance Role STAT1 gene STAT2 gene Signal Pathway Signal Transduction T-Lymphocyte Testing Therapeutic Up-Regulation Zoonoses antimicrobial blood-brain barrier crossing blood-brain barrier permeabilization brain dysfunction cell type complement pathway mouse model neglect neuron apoptosis pathogenic bacteria protective effect response synaptic pruning transcription factor transcriptome sequencing type I interferon receptor

展开

项目摘要

Project Summary/Abstract: Neurobrucellosis is the most morbid complication of Brucella infection in humans, but studies on neurobrucellosis are scarce due to the lack of relevant animal models. In this proposal, we present the first murine models of neurobrucellosis in which Brucella is able to colonize the brain, induce inflammation, and impair neurologic function. We found marked upregulation of transcriptional signatures associated with interferon (IFN) signaling and complement activation in the brains of mice with neurobrucellosis. In addition, we found that IFNs restrict neurologic complications of brucellosis. In Specific Aim #1 of this proposal, we will investigate the cell types and signaling pathways responsible for IFN-mediated protection against neurobrucellosis. In Specific Aim #2, we will investigate whether interactions between complement and IFNs are involved in the pathogenesis of neurobrucellosis. Collectively, our results will enhance our basic understanding of neurobrucellosis, and potentially identify targets for complementary therapeutics for neurobrucellosis.

项目摘要/摘要：神经核糖菌病是人类布鲁氏菌感染最病态的并发症，但由于缺乏相关的动物模型，因此缺乏关于神经性细胞增多症的研究。在此提案中，我们介绍了第一个神经核糖菌病的鼠模型，其中布鲁氏菌能够定居大脑，诱发炎症并损害神经系统功能。我们发现明显的上调与干扰素（IFN）信号传导和补体激活相关的转录特征患有神经核和神经性易素病的小鼠的大脑。此外，我们发现IFNS限制了神经系统布鲁氏菌病的并发症。在本提案的特定目的＃1中，我们将研究细胞类型以及负责IFN介导的对神经核酸异化的保护的信号通路。在特定的目标＃2，我们将调查补充与IFN之间的相互作用是涉及神经核糖菌病的发病机理。总的来说，我们的结果将增强我们的基本了解神经核细胞增多症，并有可能识别互补疗法的靶标用于神经性易生核病。