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; 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）：莱姆病和人类粒细胞性ehrllichiosis（HGE），由Borrelia burgdorferi和Anaplasma phagocytophila引起，是美国的两种常见的媒介传播疾病。 两种病原体都是由ixodes capularis tick传递给人的，并且在节肢动物和脊椎动物宿主中已记录了双重感染。 该应用的目的是确定小鼠与伯氏芽孢杆菌和吞噬曲霉的共同感染是否改变了伯格多菲利芽孢杆菌的感染性芽孢杆菌的感染力和鼠莱姆关节炎的严重程度。 我们最近发表的报告表明，用汉堡芽孢杆菌和吞噬细胞的小鼠同时进行实验感染增加了螺旋体的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的挑战剂量以及每种病原体暴露的时间如何影响鼠莱姆利氏病的进程来进一步探讨这一点。 我们还将确定当B. burgdorferi和A. phagocytophila通过tick咬伤而不是针接种时，是否会观察到这些差异。 我们已发表的研究还表明，对体内表达的爆发芽孢杆菌基因的抗体有助于抗螺旋体的免疫力，而伯格多菲尔（B. burgdorferi）基因表达可以受到宿主免疫反应的影响。 现在，我们将使用已开发的螺旋体DNA微阵列来探讨以下假设：b。burgdorferi基因表达在与吞噬细胞藻的共感染期间经体体内修饰。 我们将确定在共感染期间改变表达水平的爆发芽孢杆菌基因，并检查这些基因产物在免疫性感染和关节炎症的严重程度中的作用。 这些研究将更清楚地定义伯氏芽孢杆菌和吞噬曲霉的共同感染对鼠莱姆关节炎的过程的影响，并探索双重感染改变螺旋体感染的机制。 这些努力应加深我们对与这些tick传播药物对疾病结果的共同感染的重要性的理解，并作为双重感染如何影响宿主反应和病原体基因表达的一般模型。