CO-INFECTION WITH B BURGDORFERI AND A PHAGOCYTOPHILA

伯氏疏螺旋体和嗜吞噬细胞球菌共同感染

• 批准号: 6600861
• 负责人: Erol Fikrig
• 金额: $ 24.53万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6600861
• 关键词: Borrelia; Ixodes; Lyme disease; Rickettsiales; antibacterial antibody; arthritis; bacterial DNA; bacterial antigens; bacterial genetics; ehrlichiosis; gene expression; laboratory mouse; microarray technology; pathologic process; secondary infection

DESCRIPTION (provided by applicant): Lyme disease and human granulocytic ehrlichiosis (HGE), caused by Borrelia burgdorferi and Anaplasma phagocytophila respectively, are two common vector-borne illnesses in the United States. Both pathogens are transmitted to man by Ixodes scapularis ticks, and dual infections have been documented in the arthropod and vertebrate hosts. The purpose of this application is to determine whether co-infection of mice with B. burgdorferi and A. phagocytophila alters B. burgdorferi infectivity and the severity of murine Lyme arthritis. Our recently published report showed that the simultaneous experimental infection of mice with B. burgdorferi and A. phagocytophila increased spirochete numbers and the severity of joint inflammation. We will now explore this further by determining how the challenge dose of each organism and the timing of exposure of each pathogen influences the course of murine Lyme borreliosis. We will also determine whether these differences are observed when B. burgdorferi and A. phagocytophila are transmitted via tick bite rather than needle inoculation. Our published studies have also demonstrated that antibodies against B. burgdorferi genes that are expressed in vivo contribute to immunity against the spirochete and that B. burgdorferi gene expression can be influenced by the host immune response. We will now use spirochete DNA microarrays that we have developed to explore the hypothesis that B. burgdorferi gene expression in vivo is modified during co-infection with A. phagocytophila. We will identify B. burgdorferi genes that have altered levels of expression during co-infection and examine the role of these gene products in immunity against infection and the severity of joint inflammation. These studies will more clearly define the influence of B. burgdorferi and A. phagocytophila co-infection on the course of murine Lyme arthritis and explore the mechanisms by which dual infection alters spirochete infection. These efforts should increase our understanding of the importance of co-infection with these tick-borne agents on the outcome of disease and serve as a general model for how dual infection can influence host responses and pathogen gene expression.

描述（由申请人提供）：莱姆病和人粒细胞埃利希体病（HGE）分别由伯氏疏螺旋体和嗜吞噬细胞无形体引起，是美国两种常见的媒介传播疾病。 这两种病原体均通过肩胛硬蜱传播给人类，并且已在节肢动物和脊椎动物宿主中记录到双重感染。 本申请的目的是确定小鼠同时感染伯氏疏螺旋体和嗜吞噬细胞杆菌是否会改变伯氏疏螺旋体的感染性和鼠莱姆关节炎的严重程度。 我们最近发表的报告表明，同时感染伯氏疏螺旋体和嗜吞噬细胞球菌的小鼠实验性感染增加了螺旋体数量和关节炎症的严重程度。 现在，我们将通过确定每种生物体的攻击剂量和每种病原体的暴露时间如何影响小鼠莱姆疏螺旋体病的病程来进一步探讨这一点。 我们还将确定当伯氏疏螺旋体和嗜吞噬细胞杆菌通过蜱叮咬而不是针头接种传播时是否观察到这些差异。 我们发表的研究还表明，体内表达的针对伯氏疏螺旋体基因的抗体有助于抵抗螺旋体的免疫，并且伯氏疏螺旋体基因表达可能受到宿主免疫反应的影响。 现在，我们将使用我们开发的螺旋体 DNA 微阵列来探索伯氏疏螺旋体体内基因表达在与嗜吞噬放线菌共感染期间发生改变的假设。 我们将鉴定在共感染期间表达水平发生改变的伯氏疏螺旋体基因，并检查这些基因产物在感染免疫和关节炎症严重程度中的作用。 这些研究将更清楚地确定伯氏疏螺旋体和嗜吞噬细胞杆菌共同感染对小鼠莱姆关节炎病程的影响，并探讨双重感染改变螺旋体感染的机制。 这些努力应该增加我们对这些蜱传病原体共同感染对疾病结果的重要性的理解，并作为双重感染如何影响宿主反应和病原体基因表达的通用模型。