Salmonella enterica serovar Typhimurium induces cell death in bovine monocyte-derived macrophages by early sipB-dependent and delayed sipB-independent mechanisms

• Published in: Infection and immunity Vol. 69; no. 4; pp. 2293 - 2301
• Main Authors: SANTOS, Renato L, TSOLIS, Renée M, BÄUMLER, Andreas J, SMITH, Roger III, ADAMS, L. Garry
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.04.2001
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Animals; Apoptosis; Bacterial Proteins - physiology; Bacteriology; Biological and medical sciences; Caspases - physiology; Cattle; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; DNA Fragmentation; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics; Macrophages - microbiology; Macrophages - physiology; Membrane Proteins - physiology; Microbiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Salmonella enterica; Salmonella typhimurium - physiology; sipB gene; Systemic; Salmonella typhimurium; Systemic disease; Bacteria; Intestinal disease; Earliness; Salmonellosis; Localization; Cell; Ungulata; Enterobacteriaceae; Human; Bovine; Monocyte; Rodentia; Diarrhea; Infection; Vertebrata; Mammalia; Mouse; Cell death; Bacteriosis; Digestive diseases; Early; Artiodactyla; Apoptosis; Macrophage
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.69.4.2293-2301.2001

It was previously demonstrated that Salmonella enterica serovar Typhimurium induces cell death with features of apoptosis in murine macrophages. Mice infected with Salmonella serovar Typhimurium develop systemic disease without diarrhea, whereas the infection in cattle and in humans is localized and characterized by diarrhea. Considering these clinical disease expression differences between mice and cattle, we investigated whether serovar Typhimurium is cytotoxic for bovine macrophages. Macrophages infected with serovar Typhimurium grown in the logarithmic phase quickly underwent cell death. Macrophages infected with stationary-phase cultures or with a mutant lacking sipB underwent no immediate cell death but did develop delayed cytotoxicity, undergoing cell death between 12 and 18 h postinfection. Both pathways were temporarily blocked by the general caspase inhibitor Z-VAD-Fmk and by the caspase 1 inhibitor Z-YVAD-Fmk. Comparisons of macrophages from cattle naturally resistant or susceptible to intracellular pathogens indicated no differences between these two genetic backgrounds in terms of susceptibility to serovar Typhimurium-induced cell death. We conclude that Salmonella serovar Typhimurium induces cell death in bovine macrophages by two distinct mechanisms, early sipB-mediated and delayed sipB-independent mechanisms.