Interferons in Neurobrucellosis

神经布鲁氏菌病中的干扰素

• 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
• 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

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： 神经布鲁氏菌病是人类布鲁氏菌感染最严重的并发症，但 由于缺乏相关的动物模型，对神经布鲁氏菌病的研究很少。在这个提案中， 我们提出了第一个神经布鲁氏菌病小鼠模型，其中布鲁氏菌能够定植于 脑，诱发炎症，损害神经功能。我们发现显着上调 与干扰素 (IFN) 信号传导和补体激活相关的转录特征 患有神经布鲁氏菌病的小鼠的大脑。此外，我们发现干扰素限制神经系统 布鲁氏菌病的并发症。在该提案的具体目标#1中，我们将研究细胞类型 以及负责干扰素介导的神经布鲁氏菌病保护作用的信号通路。在 具体目标#2，我们将研究补体和干扰素之间的相互作用是否存在 参与神经布鲁氏菌病的发病机制。总的来说，我们的成果将增强我们的基础 了解神经布鲁氏菌病，并可能确定补充治疗的靶点 用于神经布鲁氏菌病。