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Updated: Oct 2, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Host immune response to Salmonella enterica serovar Typhimurium infection in mice derived from wild strains
Giovanna Sebastiani1, Véronique Blais, Vanessa Sancho
1Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1A4.
Abstract:
Studies of mouse models of endotoxemia and sepsis with gram-negative bacteria have shown that the host response is genetically controlled. Mice infected with the gram-negative bacterium Salmonella enterica serovar Typhimurium exhibit marked genetic differences in disease manifestation, and the wild-derived strain Mus musculus molossinus MOLF/Ei is extremely susceptible to S. enterica serovar Typhimurium. The kinetics of bacterial proliferation within the liver and the spleen and histological examination of tissue sections have suggested that MOLF/Ei mice do not succumb to infection because of overwhelming bacterial growth in the reticuloendothelial organs or massive tissue necrosis, as observed in other Salmonella-susceptible strains. MOLF/Ei mice respond normally to lipopolysaccharide (LPS) in vivo and in vitro, as determined by the production of tumor necrosis factor alpha and spleen cell mitogenesis. However, they have a unique cytokine profile in response to infection compared to that observed for other Salmonella-susceptible mice. There was increased expression of mRNA of the interleukin-1 alpha (IL-1 alpha) and IL-1 beta genes as the infection in the spleens and livers of MOLF/Ei mice progressed. Despite the fact that MOLF/Ei mice have the ability to respond to LPS and the fact that there are significant increases in IL-1 alpha and IL-1 beta mRNA, Nos2 in the spleen is not upregulated and nitrite production by spleen cells is reduced. At the central level, the inflammatory response is characterized by strong upregulation of the inhibitory factor kappa B alpha and Toll-like receptor 2 genes, two genes known to be regulated by LPS and IL-1 in the brain. The high levels of IL-1 expression in the spleens and livers of MOLF/Ei mice may have important implications for the activation of peripheral and central innate immune mechanisms.
Insights
Genetic factors control host response to Salmonella infection. MOLF/Ei mice show unique cytokine profiles, with high IL-1 expression but reduced Nos2, impacting innate immunity.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Host response to Gram-negative bacterial infections like Salmonella enterica serovar Typhimurium is genetically controlled.
- The wild-derived mouse strain MOLF/Ei exhibits extreme susceptibility to S. enterica serovar Typhimurium.
- Unlike other susceptible strains, MOLF/Ei mice do not succumb due to overwhelming bacterial growth or massive tissue necrosis.
Purpose of the Study:
- To investigate the genetic basis of susceptibility to Salmonella infection in MOLF/Ei mice.
- To characterize the unique immune response and cytokine profile of MOLF/Ei mice during S. enterica serovar Typhimurium infection.
Main Methods:
- Infection of MOLF/Ei mice with S. enterica serovar Typhimurium.
- Analysis of bacterial proliferation in liver and spleen.
- Histological examination of tissue sections.
- Assessment of lipopolysaccharide (LPS) response in vivo and in vitro (TNF-alpha production, spleen cell mitogenesis).
- Quantitative analysis of cytokine mRNA expression (IL-1 alpha, IL-1 beta, Nos2, NFKBIA, TLR2) in spleen and liver.
- Measurement of nitrite production by spleen cells.
Main Results:
- MOLF/Ei mice display normal responses to LPS but a distinct cytokine profile during infection.
- Increased mRNA expression of interleukin-1 alpha (IL-1 alpha) and IL-1 beta was observed in spleen and liver.
- Despite elevated IL-1, nitric oxide synthase 2 (Nos2) was not upregulated in the spleen, and nitrite production was reduced.
- Central inflammatory response showed strong upregulation of NFKBIA and Toll-like receptor 2 (TLR2) genes in the brain.
Conclusions:
- The susceptibility of MOLF/Ei mice to S. enterica serovar Typhimurium is linked to a unique cytokine profile, not overwhelming bacterial growth.
- High IL-1 expression in peripheral organs, coupled with impaired Nos2 induction, may contribute to disease pathogenesis.
- Upregulation of inhibitory factors like NFKBIA and TLR2 in the brain suggests complex central immune regulation.
- These findings highlight the critical role of IL-1 in modulating peripheral and central innate immune responses during Salmonella infection.
