Macrophage defect and inflammatory cell recruitment dysfunction in Salmonella susceptible C3H/HeJ mice.
C3H/HeJ mice are homozygous for the Lpsd allele and, as a consequence, are hyporesponsive to all of the biological effects of bacterial lipopolysaccharide (LPS) that have been studied. These mice die in the early phase of infection when inoculated with virulent Salmonella. This susceptibility is also regulated by the Lpsd allele. The mechanism of Lpsd-conferred Salmonella susceptibility was evaluated in these studies. The response of C3H/HeJ mice to S. typhimurium strains of differing virulence was compared in a series of in vivo experiments to the response of: endotoxin-responsive (Lpsn) mice that carry another Salmonella susceptibility gene (Itys) and endotoxin-responsive mice that carry a Salmonella resistance gene (Ityr). The C3H/HeJ mice (genotype Lpsd/Ityr) were more resistant than Lpsn/Itys mice to strains of S. typhimurium of reduced virulence but less resistant than Lpsn/Ityr mice. In addition, C3H/HeJ macrophages cultured in vitro were less able to contain net salmonellae multiplication than were macrophages from Lpsn/Ityr mice. Moreover, histopathological findings revealed that S. typhimurium-infected Lpsn/Ityr animals recruited an abnormally low number of cells into their livers compared to either Lpsn/Ityr mice or Lpsn/Itys mice. These data suggest that the susceptibility of C3H/HeJ mice may be the result of at least two Lpsd-encoded defects: a decreased capacity of macrophages to restrict Salmonella growth and a reduced recruitment of inflammatory cells into liver.
D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D007249:Inflammation; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium
D008070:Lipopolysaccharides