Macrophages influence Salmonella host-specificity in vivo

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 24 h. 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 4 h post-infection for both serovars. The number of Typhimurium in macrophages remained high at 4 h post-infection, but the number of Typhi in macrophages decreased substantially within 4 h 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 24 h in vitro, suggesting that the differential killing of the two serovars by macrophages requires additional factors within the host.