Salmonella infection in the murine brain

National Institute Of Allergy And Infectious Diseases

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Abstract

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.