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Updated: Mar 12, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Enhanced Salmonella mortality in naturally resistant, immunocompetent male mice is associated with an altered
Aliyah N Bennett1,2, Allysa L Cole1,2,3, John S Gunn1,2,4
1Center for Microbe & Immunity Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Abstract:
While typhoid fever affects both sexes at an equal rate, males are at a higher risk for intestinal perforation, which increases mortality. The mechanisms behind the increased morbidity of typhoid fever in human males remain an important but understudied question. Using a 129X1/SvJ (NRAMP+/+ [SLC11A1]) murine model of typhoid chronic infection, we determined that males in this model exhibit increased bacterial burden and mortality in comparison to females (median survival 7 vs 11 days post-infection, respectively). This decreased survival in males was influenced by the diet preceding infection as male mice fed a lithogenic diet, to induce gallstones important to chronic infection, or a normal diet had a lower median survival time, although no difference in the overall probability of survival was observed. We also explored how the systemic immune response may contribute to increased mortality by comparing serum cytokine levels between males and females. Males had higher overall levels of pro-inflammatory cytokines and IL-10 and lower levels of IL-27, which are known to inhibit the protective responses to Salmonella infection. Together, we present the first report that the 129X1/SvJ murine model of Salmonella infection responds to infection in a sex-dependent manner, characterized by maladjusted systemic cytokine production and increased bacterial burden in males.
Insights
Male mice show increased mortality and bacterial burden during Salmonella infection compared to females. Diet influences survival, and sex-based differences in cytokine profiles contribute to higher male mortality in this typhoid fever model.
Area of Science:
- Immunology
- Infectious Diseases
- Sex Differences in Disease
Background:
- Typhoid fever affects both sexes equally but has higher mortality in males due to complications like intestinal perforation.
- The underlying mechanisms driving increased male morbidity in typhoid fever are not well understood.
- Salmonella Typhi is the causative agent of typhoid fever.
Purpose of the Study:
- To investigate sex-based differences in response to Salmonella infection using a murine model.
- To explore the role of diet and systemic immune response in male susceptibility to typhoid fever.
Main Methods:
- Utilized a 129X1/SvJ murine model (NRAMP+/+ [SLC11A1]) for chronic Salmonella infection.
- Compared bacterial burden, mortality rates, and survival times between male and female mice.
- Analyzed serum cytokine levels (pro-inflammatory cytokines, IL-10, IL-27) in relation to sex and infection outcome.
- Investigated the impact of diet (lithogenic vs. normal) on male survival.
Main Results:
- Male mice exhibited significantly increased bacterial burden and reduced median survival time (7 days) compared to females (11 days).
- Diet influenced male survival, with both lithogenic and normal diets leading to lower median survival, though overall survival probability was not affected.
- Males displayed higher systemic levels of pro-inflammatory cytokines and IL-10, alongside lower levels of IL-27, compared to females.
Conclusions:
- The 129X1/SvJ murine model demonstrates sex-dependent responses to Salmonella infection.
- Maladjusted systemic cytokine production and increased bacterial burden in males contribute to higher mortality.
- This study highlights the importance of sex as a biological variable in infectious disease research.
