Salmonella infection in the murine brain

这项研究的目的是利用鼠伤寒沙门氏菌感染的小鼠模型来研究细菌性脑膜炎。我们正在使用各种小鼠品系，这些品系在遗传上对感染鼠伤寒沙门氏菌的易感性不同。由于自然耐药相关巨噬细胞蛋白1(NRAMP1)的失活突变，C57BL/6小鼠非常敏感。Nramp1对巨噬细胞功能具有多效性，在控制包括鼠伤寒沙门氏菌在内的几种细胞内细菌病原体中发挥重要作用。将遗传易感的Nramp1-/-C57BL/6小鼠与Nramp+/+重组C57BL/6小鼠进行比较，后者在几周内发展为可控的持续感染。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+/+小鼠的脑中分离到活的沙门氏菌。少数Nramp1+/+小鼠出现严重的共济失调，大脑中的细菌负荷非常高(比任何其他小鼠高出2-3个对数)，并出现严重的脑膜脑炎、血管炎和脓肿的组织学迹象，所有这些都是人类沙门氏菌脑膜炎的特征。

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.