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

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 witho ut diarrhea, whereas the infection in cattle and in humans is localized and characterized by diarrhea. Considering these clinical disease expression d ifferences between mice and cattle, we investigated whether serovar Typhimu rium is cytotoxic for bovine macrophages. Macrophages infected with serovar Typhimurium grown in the logarithmic phase quickly underwent cell death. M acrophages infected with stationary-phase cultures or with a mutant lacking sipB underwent no immediate cell death but did develop delayed cytotoxicit y, undergoing cell death between 12 and 18 h postinfection. Both pathways w ere temporarily blocked by the general caspase inhibitor Z-VAD-Fmk and by t he caspase 1 inhibitor Z-YVAD Fmk. Comparisons of macrophages from cattle n aturally resistant or susceptible to intracellular pathogens indicated no d ifferences between these two genetic backgrounds in terms of susceptibility to serovar Typhimurium-induced cell death. We conclude that Salmonella ser ovar Typhimurium induces cell death in bovine macrophages by two distinct m echanisms, early sipB mediated and delayed sipB-independent mechanisms.