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Macrophage defect and inflammatory cell recruitment dysfunction in Salmonella susceptible C3H/HeJ mice
Abstract:
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.
Insights
C3H/HeJ mice with the Lpsd allele show increased susceptibility to Salmonella infection due to impaired macrophage function and reduced inflammatory cell recruitment in the liver. This highlights genetic defects influencing Salmonella pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- C3H/HeJ mice possess the Lpsd allele, leading to hyporesponsiveness to bacterial lipopolysaccharide (LPS).
- These mice exhibit increased mortality during virulent Salmonella infections, a susceptibility linked to the Lpsd allele.
Purpose of the Study:
- To elucidate the mechanism underlying Lpsd-conferred susceptibility to Salmonella infection.
- To compare the response of C3H/HeJ mice to Salmonella typhimurium with that of other mouse strains.
Main Methods:
- In vivo experiments comparing C3H/HeJ mice (Lpsd/Ityr) with endotoxin-responsive mice (Lpsn/Itys and Lpsn/Ityr) against S. typhimurium strains of varying virulence.
- In vitro macrophage cultures to assess Salmonella containment.
- Histopathological analysis of liver tissues from infected mice.
Main Results:
- C3H/HeJ mice showed intermediate resistance to less virulent S. typhimurium strains compared to control groups.
- Macrophages from C3H/HeJ mice exhibited reduced ability to restrict Salmonella multiplication in vitro.
- S. typhimurium-infected C3H/HeJ mice displayed lower inflammatory cell recruitment in the liver.
Conclusions:
- Salmonella susceptibility in C3H/HeJ mice is attributed to at least two Lpsd-encoded defects.
- These defects include a diminished macrophage capacity to restrict bacterial growth and reduced inflammatory cell infiltration in the liver.