title: Salmonella Meningitis Associated with Monocyte Infiltration in Mice.
abstract: In the current study, we examined the ability of Salmonella enterica serovar Typhimurium to infect the central nervous system and cause meningitis following the natural route of infection in mice. C57BL/6J mice are extremely susceptible to systemic infection by Salmonella Typhimurium because of loss-of-function mutations in Nramp1 (SLC11A1), a phagosomal membrane protein that controls iron export from vacuoles and inhibits Salmonella growth in macrophages. Therefore, we assessed the ability of Salmonella to disseminate to the central nervous system (CNS) after oral infection in C57BL/6J mice expressing either wild-type (resistant) or mutant (susceptible) alleles of Nramp1. In both strains, oral infection resulted in focal meningitis and ventriculitis with recruitment of inflammatory monocytes to the CNS. In susceptible Nramp1-/-mice, there was a direct correlation between bacteremia and the number of bacteria in the brain, which was not observed in resistant Nramp1+/+mice. A small percentage of Nramp1+/+mice developed severe ataxia, which was associated with high bacterial loads in the CNS as well as clear histopathology of necrotizing vasculitis and hemorrhage in the brain. Thus, Nramp1 is not essential for Salmonella entry into the CNS or neuroinflammation, but may influence the mechanisms of CNS entry as well as the severity of meningitis.
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bauler
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Tregei
authors.initials: T
authors.lastname: Starr
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado.
authors.forename: Toni A
authors.initials: TA
authors.lastname: Nagy
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Dana
authors.initials: D
authors.lastname: Scott
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Clayton W
authors.initials: CW
authors.lastname: Winkler
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Olivia
authors.initials: O
authors.lastname: Steele-Mortimer
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado.
authors.forename: Corrella S
authors.initials: CS
authors.lastname: Detweiler
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana. Electronic address: petersonka@niaid.nih.gov.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Peterson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001259:Ataxia / Q000378:metabolism / Q000473:pathology; D016470:Bacteremia / Q000150:complications / Q000382:microbiology / Q000473:pathology; D001921:Brain / Q000382:microbiology / Q000473:pathology; D027682:Cation Transport Proteins / Q000172:deficiency / Q000378:metabolism; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000473:pathology; D015169:Colony Count, Microbial; D004660:Encephalitis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008581:Meningitis / Q000150:complications / Q000382:microbiology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology*; D020556:Neutrophil Infiltration; D012481:Salmonella Infections, Animal / Q000150:complications / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000502:physiology*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1