Borrelia miyamotoi meningioencephalitis

脑膜是中枢神经系统感染后免疫细胞运输的重要介质。 系统（CNS）。最近发现的蜱传播的人类病原体，宫本疏螺旋体，引起急性发热， 疾病，并可能有严重的并发症，免疫功能低下的患者。具体来说，这些患者 缺乏B细胞并在感染B后发展为脑膜脑炎。宫本井。我们的长期目标是 确定与严重疏螺旋体相关的神经病理学基础的生理机制 宫本氏病（BMD）。我们的中心假设是B。脑膜的Miyamotoi定植通常 仅在缺乏B细胞的情况下发生。我们将通过2个具体目标来解决这个假设：1）确定 B动力学在没有B细胞的情况下，miyamotoi播散到脑膜中;和，2）鉴定免疫 有助于病原体控制的反应。在本提案的目标1中，我们将确定a）以下物质的动力学： 脑膜感染; B）接种部位变化的影响;以及c）空间和时间定殖 脑膜感染的模式在目标2中，我们将确定T依赖性B细胞应答的作用; 脑小胶质细胞活化对B反应的变化。宫本感染。这些目标的实现将决定 B的动力学。并将确定B细胞反应是否确实是 需要控制感染。总的来说，这项建议与国家影响和发展研究所的使命有关，因为 对严重BMD的了解将使医疗保健提供者能够针对高危患者提供以下信息： 他们的条件和预防策略，以避免BMD和其他蜱传 疾病

The meninges are important mediators of immune cell trafficking in response to infection in the central nervous system (CNS). A recently identified tick-borne human pathogen, Borrelia miyamotoi, causes an acute febrile illness, and may have serious complications in immunocompromised patients. Specifically, these patients are deficient in B cells and develop meningoencephalitis upon infection with B. miyamotoi. Our long-term goal is to determine the physiological mechanisms that underlie the neuropathologies associated with severe Borrelia miyamotoi disease (BMD). Our central hypothesis is that B. miyamotoi colonization of the meninges routinely occurs only in the absence of B cells. We will address this hypothesis with 2 Specific Aims: 1) Determining the kinetics of B. miyamotoi dissemination into the meninges in the absence of B cells; and, 2) Identifying immune responses that contribute to pathogen control. In Aim 1 of this proposal we will determine a) the kinetics of meningeal infection; b) the effects of inoculation site variation; and c) the spatial and temporal colonization patterns of meningeal infection. In Aim 2, we will determine the role of T-dependent B cell responses; and changes in brain microglial activation in response to B. miyamotoi infection. Completion of these aims will define the kinetics of B. miyamotoi colonization of the meninges and will determine if B cell responses are indeed required for control of infection. Overall, this proposal is relevant to the mission of NIAID because a greater understanding of severe BMD will enable healthcare providers to target at-risk patients with information about alternative treatments for their conditions and preventative strategies to avoid BMD and other tick-borne diseases.