Interferons in Neurobrucellosis

项目概要/摘要： 神经性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，对神经型布鲁氏菌病的研究很少。在这一提议中， 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殖于 脑，诱发炎症，并损害神经功能。我们发现， 与干扰素（IFN）信号传导和补体激活相关的转录特征， 神经布鲁氏菌病小鼠的大脑。此外，我们发现干扰素限制了神经功能， 布鲁氏菌病的并发症在本提案的具体目标#1中，我们将研究细胞类型 和负责IFN介导的抗神经布鲁氏菌病保护的信号通路。在 具体目标#2，我们将研究补体和IFN之间的相互作用是否是 参与神经布鲁氏菌病的发病机制。总的来说，我们的成果将加强我们的基本 了解神经布鲁氏菌病，并可能确定补充治疗的靶点 神经布鲁氏菌病

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.