LYME DISEASE--HOST PARASITE INTERACTIONS

莱姆病——宿主寄生虫相互作用

• 批准号: 6163958
• 负责人: STEPHEN E. MALAWISTA
• 金额: $ 31.01万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-15 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6163958
• 关键词: Borrelia; Lyme disease; bacteria infection mechanism; bactericidal immunity; cellular immunity; free radicals; gene expression; genetic strain; human subject; in situ hybridization; laboratory mouse; leukocyte activation /transformation; macrophage; phagocytosis; phlebotomy; polymerase chain reaction; virulence

DESCRIPTION: (Adapted from the applicant's abstract) - Understanding the capacity of the cellular immune response to clear Borrelia, the etiologic agent of Lyme disease, is essential to a proper understanding of the pathogenesis of this disorder. We know that both neutrophils and macrophages take up and kill Borrelia rapidly in vitro. Yet, intact spirochetes can be observed in skin and other tissues, and have been isolated from uninflamed peritoneal cavity despite the presence of resident macrophages. In order to examine the failure of phagocytes to clear the spirochetes in vivo, the killing mechanisms of phagocytes will be characterized. In situ microscopic examination of spirochete- phagocyte interactions, in situ hybridization and ex vivo RT-PCR of cytokine and other genes will be used to establish a profile of the macrophages' state of activation and deactivation. Different strains of Borrelia will be used to elucidate mechanisms of clearance versus persistence in vivo. Finally, it is proposed to use cDNA arrays to examine differences in host gene expression patterns during activation of neutrophils and macrophages by these types of Borrelia. These studies may provide the technical and conceptual basis for improvements in diagnostic and prognostic aspects of inflammatory diseases.

描述：（改编自申请人的摘要）- 理解 细胞免疫反应清除疏螺旋体的能力 莱姆病的病因对于正确理解至关重要 这种疾病的发病机制。我们知道，中性粒细胞和 巨噬细胞在体外迅速吞噬并杀死疏螺旋体。然而，完好无损 螺旋体可以在皮肤和其他组织中观察到，并且已被证实 尽管存在，但仍与未发炎的腹膜腔隔离 常驻巨噬细胞。为了检查吞噬细胞是否无法 清除体内螺旋体，吞噬细胞的杀伤机制 被表征。螺旋体的原位显微镜检查 吞噬细胞相互作用、原位杂交和离体 RT-PCR 细胞因子和其他基因将用于建立细胞因子的概况 巨噬细胞的激活和失活状态。不同菌株 疏螺旋体将用于阐明清除机制 体内持久性。最后，建议使用cDNA阵列 检查激活过程中宿主基因表达模式的差异 这些类型的疏螺旋体对中性粒细胞和巨噬细胞的影响。这些研究 可以为改进提供技术和概念基础 炎症性疾病的诊断和预后方面。