Salmonella infection in the murine brain

小鼠大脑中的沙门氏菌感染

• 批准号: 10272212
• 负责人: Olivia Steele-Mortimer
• 金额: $ 71.2万
• 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/10272212
• 关键词: AIDS/HIV problem; Affect; Africa South of the Sahara; Appearance; Bacteria; Bacterial Meningitis; Biological Models; Blood - brain barrier anatomy; Blood Vessels; Brain; C57BL/6 Mouse; Cells; Dendritic Cells; Development; Encephalitis; Extravasation; Genetic Determinism; Genetic Diseases; Goals; Gram-Negative Bacteria; Human; Immunologic Deficiency Syndromes; Infection; Iron; Laboratory mice; Malaria; Malnutrition; Meninges; 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; cytokine; intravenous administration; macrophage; mouse model; mutant; 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 bacteria can be isolated from the brains and CSF of both Nramp1-/- and Nramp1+/+ mice within 3-6 days. Changes observed in the meninges include; leakage of blood vessels, increase in the number and distribution of Iba1+ cells, appearance of intracellular Salmonella and induction of cytokines. By comparing genetically resistant and susceptible mouse strains, as well as Salmonella mutants, we hope to identify the key steps in bacterial meningitis.

该研究的目的是利用感染鼠伤寒沙门氏菌的小鼠模型来研究细菌性脑膜炎。我们使用的各种小鼠品系对鼠伤寒沙门氏菌感染具有不同的遗传敏感性。由于天然耐药相关巨噬细胞蛋白 1 (NRAMP1) 的失活突变，C57BL/6 小鼠非常容易受到影响。 Nramp1 对巨噬细胞功能发挥多效性作用，并在控制包括鼠伤寒沙门氏菌在内的多种细胞内细菌病原体中发挥重要作用。正在将遗传易感性 Nramp1-/- C57BL/6 小鼠与 Nramp+/+ 重组 C57BL/6 小鼠进行比较，后者在数周内形成受控持续感染。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+/+ 小鼠的大脑和脑脊液中分离出活细菌。脑膜中观察到的变化包括：血管渗漏、Iba1+细胞数量和分布增加、细胞内沙门氏菌出现和细胞因子诱导。通过比较具有遗传抗性和易感性的小鼠品系以及沙门氏菌突变体，我们希望确定细菌性脑膜炎的关键步骤。