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Updated: May 13, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Salmonella enterica causes more severe inflammatory disease in C57/BL6 Nramp1G169 mice than Sv129S6 mice
D E Brown1, S J Libby, S M Moreland
1Massachusetts General Hospital, Harvard Medical School, 149 13th St, Boston, MA 02129, USA.
Abstract:
Salmonella enterica serovar Typhimurium (S. Typhimurium) causes systemic inflammatory disease in mice by colonizing cells of the mononuclear leukocyte lineage. Mouse strains resistant to S. Typhimurium, including Sv129S6, have an intact Nramp1 (Slc11a1) allele and survive acute infection, whereas C57/BL6 mice, homozygous for a mutant Nramp1 allele, Nramp1(G169D) , develop lethal infections. Restoration of Nramp1 (C57/BL6 Nramp1(G169) ) reestablishes resistance to S. Typhimurium; mice survive at least 3 to 4 weeks postinfection. Since many transgenic mouse strains are on a C57/BL6 genetic background, C57/BL6 Nramp1(G169) mice provide a model to examine host genetic determinants of resistance to infection. To further evaluate host immune response to S. Typhimurium, we performed comparative analyses of Sv129S6 and C57/BL6 Nramp1(G169) mice 3 weeks following oral S. Typhimurium infection. C57/BL6 Nramp1(G169) mice developed more severe inflammatory disease with splenic bacterial counts 1000-fold higher than Sv129S6 mice and relatively greater splenomegaly and blood neutrophil and monocyte counts. Infected C57/BL6 Nramp1(G169) mice developed higher proinflammatory serum cytokine and chemokine responses (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-2 and monocyte chemotactic protein-1 and chemokine [C-X-C motif] ligand 1, respectively) and marked decreases in anti-inflammatory serum cytokine concentrations (IL-10, IL-4) compared with Sv129S6 mice postinfection. Splenic dendritic cells and macrophages in infected compared with control mice increased to a greater extent in C57/BL6 Nramp1(G169) mice than in Sv129S6 mice. Overall, data show that despite the Nramp1 gene present in both strains, C57/BL6 Nramp1(G169) mice develop more severe, Th1-skewed, acute inflammatory responses to S. Typhimurium infection compared with Sv129S6 mice. Both strains are suitable model systems for studying inflammation in the context of adaptive immunity.
Insights
Salmonella Typhimurium infection causes severe inflammation in C57/BL6 mice with a mutant Nramp1 gene. Resistant Sv129S6 mice show milder responses, highlighting Nramp1
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Salmonella enterica serovar Typhimurium (S. Typhimurium) causes systemic inflammatory disease.
- The Nramp1 (Slc11a1) gene plays a crucial role in resistance to S. Typhimurium infection.
- Mouse strain genetic background influences susceptibility and immune response to S. Typhimurium.
Purpose of the Study:
- To compare the host immune response to S. Typhimurium infection in Sv129S6 and C57/BL6 Nramp1(G169) mice.
- To evaluate the role of Nramp1 in modulating inflammatory disease severity.
- To establish C57/BL6 Nramp1(G169) mice as a model for studying host genetic determinants of infection resistance.
Main Methods:
- Oral S. Typhimurium infection of Sv129S6 and C57/BL6 Nramp1(G169) mice.
- Comparative analysis of bacterial load, splenomegaly, and leukocyte counts.
- Measurement of serum cytokine and chemokine profiles.
- Assessment of splenic dendritic cell and macrophage populations.
Main Results:
- C57/BL6 Nramp1(G169) mice exhibited significantly higher splenic bacterial counts and splenomegaly compared to Sv129S6 mice.
- Infected C57/BL6 Nramp1(G169) mice showed elevated pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-2) and reduced anti-inflammatory cytokines (IL-10, IL-4).
- Greater expansion of splenic dendritic cells and macrophages was observed in C57/BL6 Nramp1(G169) mice post-infection.
Conclusions:
- Despite possessing the Nramp1 gene, C57/BL6 Nramp1(G169) mice develop a more severe, Th1-skewed inflammatory response to S. Typhimurium.
- Both mouse strains serve as valuable models for investigating inflammation and adaptive immunity during S. Typhimurium infection.
- Nramp1 genotype significantly impacts the acute inflammatory response and disease outcome in S. Typhimurium infection.
