LYME DISEASE--HOST PARASITE INTERACTIONS

描述：(改编自申请人的摘要)-了解 清除疏螺旋体的细胞免疫反应能力， 莱姆病的病因，是正确理解莱姆病的关键 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 可以在皮肤和其他组织中观察到螺旋体，并已被 从未发炎的腹膜腔分离出来，尽管存在 常驻巨噬细胞。为了检查吞噬细胞不能 清除体内的螺旋体，吞噬细胞的杀伤机制将 被刻画出来。螺旋体的原位显微镜检查- 巨噬细胞相互作用、原位杂交和体外RT-PCR 细胞因子和其他基因将被用来建立一个图谱 巨噬细胞的激活和失活状态。不同品系的 疏螺旋体将被用来阐明清除与 体内持久力。最后，提出了利用基因芯片技术来 检测激活期间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 可为改进 炎症性疾病的诊断和预后方面。

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.