Early Host Responses During Co-Infection of Tick-Borne Pathogens

总结。莱姆病病例在过去十年中增加了200%以上。抗生素疗法是 通常是有效的，尽管许多患者会经历长期的并发症，目前还不知道为什么有些患者 患者会患上慢性关节炎和神经系统损害。伯氏疏螺旋体，致病因子 引起莱姆病，是由扁虱媒介肩部硬蜱携带的。除了传播莱姆病 一、肩胛虫携带和传播其他微生物，包括埃利希菌、巴贝斯虫、无浆体、 以及病毒病原体。这一点很重要，因为扁虱传播的混合感染的患者通常表现出更多 严重的症状。目前尚不清楚宿主先天免疫系统如何处理多种病原体类型。 同时。我们建议研究早期先天髓系细胞在控制伯氏杆菌感染中的作用。 同时感染病原体的小鼠，这些病原体也是由我肩周炎传播的。根据初步数据，我们 假设共同感染病原体会引起不能控制伯氏杆菌的髓系反应 感染并导致更大的传播。这一点很重要，因为防止传播会减少 罹患慢性病的可能性。我们的初步数据显示血液中性粒细胞减少 与小鼠相比，同时感染BB和胞内细菌的小鼠的血小板 仅感染伯氏杆菌一人。我们提出了两个相关但独立的目标。在目标1中，我们将调查 由混合感染引起的中性粒细胞减少对伯氏杆菌传播的特殊作用。在目标2中，我们解决了 血小板减少和血小板对伯氏杆菌传播的影响。这项概念验证工作将 阐述感染一种病原体如何增强另一种病原体的感染和传播 在虱子传播的共同感染期间。大脑和心脏等组织的传播和感染增强 导致长期并发症易感性的严重早期事件。从这些网站了解到的信息 研究将确定宿主防御硬虱传播的联合感染的机制，并最终可能导致 预防伯氏杆菌传播的新疗法，将减少长期并发症，如 心脏炎和关节炎。

Summary. Lyme Disease cases have increased more than 200% in the last decade. Antibiotic therapy is often effective, though many patients experience long-lasting complications, and it is not yet known why some patients develop chronic arthritis and neurologic involvement. Borrelia burgdorferi senso lato, the agent that causes Lyme Disease, is carried by the tick vector Ixodes scapularis. In addition to transmitting Lyme Disease I. scapularis carries and transmits other microorganisms, including species of Ehrlichia, Babesia, Anaplasma, as well as viral pathogens. This is significant as patients with tick-borne co-infections often exhibit more severe symptoms. It is currently unclear how the host innate immune system handles multiple pathogen types simultaneously. We propose to examine the impact of early innate myeloid cells on control of B. burgdorferi in mice co-infected with pathogens that are also transmitted by I. scapularis. Based on preliminary data we hypothesize that co-infecting pathogens elicit myeloid responses that are not able to control B. burgdorferi infection and result in enhanced dissemination. This is important because preventing dissemination reduces the probability of developing chronic disease. Our preliminary data demonstrate reduced blood neutrophils and platelets in mice co-infected with both Bb and an intracellular organism Ehrlichia muris, relative to mice infected with B. burgdorferi alone. We propose two related, but independent aims. In Aim 1 we will investigate the specific role of neutropenia, induced by co-infection, on B. burgdorferi dissemination. In Aim 2 we address the impact of thrombocytopenia and platelets on B. burgdorferi dissemination. This proof-of-concept work will address how infection with one pathogen enhances the infection, and dissemination, of another pathogen during tick-borne co-infection. Enhanced dissemination and infection of such tissues as the brain and heart are critical early events that induce susceptibility to long term complications. Information learned from these studies will define mechanisms of host defense against tick-borne co-infection, and may ultimately lead to novel therapies to prevent B. burgdorferi dissemination, which will reduce long-term complications such as carditis and arthritis.