Macrophages influence Salmonella host-specificity in vivo
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Updated: Jun 21, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Tong Xu1, Stanley Maloy, Kathleen L McGuire
1Department of Biology, Molecular Biology Institute, Center for Microbial Sciences, San Diego State University, San Diego, CA 92182-4614, USA.
Abstract:
The generalist Salmonella enterica serovar Typhimurium causes disease in many animal species, but the closely related host-specific serovar Typhi only causes disease in humans. Typhi and Typhimurium share major virulence loci; hence it is not known exactly why Typhi does not cause disease in mice. We tested the hypothesis that macrophages contribute to Salmonella host-specificity in mice. No significant difference in survival of the two serovars was observed in vitro in mouse macrophage cell lines and primary murine peritoneal and bone marrow-derived macrophages after 24h. In contrast, differential survival was observed following infection in vivo. When BALB/c mice were infected intraperitoneally (i.p.), both Typhi and Typhimurium induced neutrophil influx into the peritoneum and macrophages were the major cell type containing internalized bacteria at 0.5 and 4h post-infection for both serovars. The number of Typhimurium in macrophages remained high at 4h post-infection, but the number of Typhi in macrophages decreased substantially within 4h after i.p. infection. These results indicate that macrophages are able to distinguish Typhi from Typhimurium when infected in vivo but no significant differences were observed after 24h in vitro, suggesting that the differential killing of the two serovars by macrophages requires additional factors within the host.
Insights
Salmonella Typhi and Salmonella Typhimurium survival in mouse macrophages differs in vivo, not in vitro. Macrophages distinguish between these Salmonella serovars within the host, impacting Salmonella host-specificity.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Salmonella enterica serovar Typhimurium is a generalist pathogen, while Salmonella enterica serovar Typhi is a human-specific pathogen.
- Despite sharing virulence factors, the reason for Typhi's inability to cause disease in mice remains unclear.
Purpose of the Study:
- To investigate the role of macrophages in Salmonella host-specificity.
- To determine if macrophages differentiate between S. Typhi and S. Typhimurium in mice.
Main Methods:
- In vitro studies using mouse macrophage cell lines and primary macrophages.
- In vivo infection models using BALB/c mice, with intraperitoneal administration of S. Typhi and S. Typhimurium.
- Analysis of bacterial survival within macrophages at different time points post-infection.
Main Results:
- No significant difference in S. Typhi and S. Typhimurium survival was observed in vitro after 24 hours.
- In vivo, macrophages contained high numbers of S. Typhimurium but significantly fewer S. Typhi within 4 hours post-infection.
- Both serovars induced neutrophil influx, with macrophages being the primary host cells for bacteria.
Conclusions:
- Mouse macrophages can distinguish between S. Typhi and S. Typhimurium in vivo.
- The differential killing of Salmonella serovars by macrophages in vivo suggests the involvement of additional host factors.
- Macrophages play a crucial role in determining Salmonella host-specificity.
