Salmonella infection in the murine brain

小鼠大脑中的沙门氏菌感染

• 批准号: 10014229
• 负责人: Olivia Steele-Mortimer
• 金额: $ 68.1万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10014229
• 关键词: AIDS/HIV problem; Abscess; Affect; Africa South of the Sahara; Ataxia; Bacteria; Bacterial Meningitis; Biological Models; Blood - brain barrier anatomy; Brain; C57BL/6 Mouse; Cells; Characteristics; Dendritic Cells; Development; Encephalitis; Genetic Determinism; Genetic Diseases; Goals; Gram-Negative Bacteria; Histologic; Human; Immunologic Deficiency Syndromes; Infection; Iron; Laboratory mice; Malaria; Malnutrition; Meningitis; Mouse Strains; Mus; Mutation; Neuraxis; Oral Administration; Play; Predisposition; Resistance; Role; Salmonella; Salmonella enterica; Salmonella infections; Salmonella typhimurium; Sickle Cell Anemia; Systemic disease; T-Lymphocyte; Vasculitis; intravenous administration; macrophage; mouse model; natural resistance-associated macrophage protein 1; neutrophil; pathogenic bacteria; pleiotropism; reconstitution; trait

The purpose of the study is to investigate bacterial meningitis using a mouse model of infection with Salmonella Typhimurium. We are using various mouse strains that have genetically different susceptibilities to infection with Salmonella Typhimurium. C57BL/6 mice are very susceptible due to an inactivating mutation in the natural resistance-associated macrophage protein 1 (NRAMP1). Nramp1 exerts pleiotropic effects on macrophage functions and plays an important role in the control of several intracellular bacterial pathogens including Salmonella Typhimurium. Genetically susceptible Nramp1-/- C57BL/6 mice are being compared to Nramp+/+ reconstituted C57BL/6 mice that develop a controlled sustained infection over several weeks. Following oral or intravenous administration of Salmonella Typhimurium, viable can be isolated Salmonella from the brains of both Nramp1-/- and Nramp1+/+ mice within 3-6 days. A small number of Nramp1+/+ mice develop severe ataxia and have very high bacterial burdens in the brain (2-3 logs higher than in any others) and histological signs of severe meningioencephalitis, vasculitis and abscesses, all of which are characteristic of Salmonella meningitis in humans.

本研究的目的是利用鼠伤寒沙门菌感染的小鼠模型来研究细菌性脑膜炎。我们使用了不同的小鼠品系，它们对鼠伤寒沙门氏菌的感染具有不同的基因敏感性。由于天然耐药相关巨噬细胞蛋白1 （NRAMP1）失活突变，C57BL/6小鼠非常易感。Nramp1对巨噬细胞功能具有多效性作用，在控制鼠伤寒沙门菌等多种胞内致病菌中发挥重要作用。遗传易感的Nramp -/- C57BL/6小鼠与Nramp+/+重组C57BL/6小鼠进行了比较，后者在数周内发生可控的持续感染。口服或静脉注射鼠伤寒沙门氏菌后，可在3-6天内从Nramp1-/-和Nramp1+/+小鼠的大脑中分离出沙门氏菌。少数Nramp1+/+小鼠出现严重的共济失调，大脑中细菌负担非常高（比其他小鼠高2-3个logs），并出现严重脑膜脑炎、血管炎和脓肿的组织学征象，所有这些都是人类沙门氏菌脑膜炎的特征。