USE OF SCID & IMMUNOCOMPETENT MICE TO ANALYZE PATHOGENESIS OF ORAL LISTERIOSIS

SCID 的使用

• 批准号: 6576602
• 负责人: JOHN J CEBRA
• 金额: $ 28.24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2003-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6576602
• 关键词: Listeria; Listeria infections; SCID mouse; bacteria infection mechanism; bacterial cytopathogenic effect; basement membrane; blood brain barrier; central nervous system disorders; dendrites; disease /disorder model; enzyme linked immunosorbent assay; gastrointestinal epithelium; genetically modified animals; gut associated lymphoid tissue; host organism interaction; immunoglobulin A; intracellular transport; laboratory mouse; mucosal immunity; oral mucosa; photomicrography; radioimmunoassay; tissue /cell culture; virulence

Project 1: Use of Severe Combined Immunodeficient and Immunocompetent Mice to Analyze the Pathogenesis of Oral Listeriosis (and CNS-Disease) We propose to use Severe Combined Immunodeficient (scid) and Immunocompetent (imcomp) mice, either conventionally reared (CNV) or with no gut microbial flora (GF, germ free) as models to analyze the pathogenesis or oral infection by L. monocytogenes and the host response to such gut mucosal challenge. L. monocytogenes is an opportunistic, sometimes fatal, pathogen of humans and a more common pathogen of domestic food animals. We have developed the first laboratory animal model for Central Nervous System (CNS)-listeriosis following oral infection. Oral infection of CNV scid mice with 'wild-type' L. monocytogenes results in CNS-infection and symptoms--classically 'circling disease' and death within 14-21 days. We plan to use 'wild-type' virulent L. monocytogenes, and four virulence- factor negative ('knock-out') strains of L.monocytogenes to probe the mechanisms of pathogenesis via the gut mucosal route and the role the elements of the host's mucosal immune system may play to prevent, contain, and resolve gut mucosal infections. We believe our finds may be relevant to understanding and immunizing versus gut mucosal infections. We believe our findings may be relevant to understand and immunizing versus gut mucosal infections by many facultative, intracellular bacterial pathogens. We aim to: 1) analyze how oral/gut mucosal L. monocytogenes can translocate the gut, disseminate and transit the blood-brain barrier; 2) evaluate which elements of the host's mucosal immune system may act to prevent and limit infection; 3) determine whether 'innate' or 'natural' immune mechanisms may be effecting at limiting infection by the gut mucosal route; 4) use L. monocytogenes mucosal infections as a model for evaluating whether secretory IgA Abs can effectively contain an infection of the mucosal epithelium by a bacterial intracellular pathogen.

项目1：使用严重组合的免疫缺陷和免疫能力小鼠 分析口服李斯特氏病的发病机理（和CNS-疾病） 我们建议使用严重的联合免疫缺陷剂（SCID）和 免疫能力（IMCOMP）小鼠，无论是常规饲养（CNV）还是与 没有肠道微生物菌群（无gf，胚芽）作为模型来分析 发病机理或单核细胞增生和宿主反应的口服感染 应对这种肠粘膜挑战。 L.单核细胞增生是一种机会主义， 有时人类致命的病原体和家庭的更常见病原体 食用动物。我们已经开发了第一个用于 口腔感染后的中枢神经系统（CNS） - 子宫病。口服 用“野生型”单核细胞增生植物感染CNV SCID小鼠会导致 中枢神经系统感染和症状 - 经典的“围绕疾病”和死亡 在14-21天内。 我们计划使用“野生型”毒力单核细胞增生和四个毒力 - l. mumocytogenes菌株因子负（“敲除”）探测 通过肠粘膜途径和作用的发病机理机理 宿主的粘膜免疫系统的元素可能会播放，以防止，包含， 并解决肠粘膜感染。我们相信我们的发现可能很重要 了解和免疫与肠粘膜感染。我们相信 我们的发现可能与理解和免疫与肠道有关 许多辅助，细胞内细菌病原体的粘膜感染。 我们的目的是：1）分析口服/肠粘膜单核细胞增生剂如何 将肠道易位，传播并越过血脑屏障； 2） 评估宿主的粘膜免疫系统的哪些元素可以起作用 预防和限制感染； 3）确定“先天”还是“自然” 免疫机制可能会在肠道限制感染时产生 粘膜路线； 4）使用单核细胞增生李斯特氏菌粘膜感染作为模型 评估分泌的IgA ABS是否有效地包含感染 细菌细胞内病原体的粘膜上皮。