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

项目1：使用严重联合免疫缺陷和免疫活性的小鼠 口腔李斯特菌病(及中枢神经系统病)的发病机制分析 我们建议使用严重联合免疫缺陷(SCID)和 免疫活性(IMCOMP)小鼠，常规饲养(CNV)或 没有肠道微生物区系(GF，无菌)作为模型来分析 单核细胞增多性乳杆菌口腔感染的发病机制和宿主反应 对这种肠道粘膜的挑战。单核细胞增多性乳杆菌是一种机会主义的， 有时是致命的，是人类的病原体，也是一种更常见的家用病原体 食用动物。我们开发了第一个实验动物模型，用于 中枢神经系统(CNS)-口腔感染后的李斯特菌病。口头的 CNV SCID小鼠感染野生型单核细胞增多性乳杆菌 中枢神经系统感染和症状--经典的“循环病”和死亡 在14-21天内。 我们计划使用‘野生型’毒力的单核细胞增多性李斯特菌，以及四种毒力- 因子阴性(‘敲除’)的单核细胞增多性李斯特氏菌 肠粘膜途径的致病机制及其作用 宿主粘膜免疫系统的成分可能起到预防、遏制、 并解决肠道粘膜感染。我们相信我们的发现可能与 了解和免疫与肠道粘膜感染的对比。我们相信 我们的发现可能与理解和免疫与肠道有关 许多兼性的、细胞内的细菌引起的粘膜感染。 我们的目标是：1)分析口腔/肠道粘膜中单核细胞增多性乳杆菌 移位肠道，扩散和转运血脑屏障；2) 评估宿主粘膜免疫系统的哪些成分可能作用于 预防和限制感染；3)确定是“天生的”还是“自然的” 免疫机制可能在限制肠道感染方面发挥作用 粘膜途径；4)以单核细胞增多性乳杆菌粘膜感染为模型 评估分泌型IgA抗体是否能有效抑制感染 由细菌细胞内病原体引起的粘膜上皮损伤。

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.