THE SALMONELLA VIRULENCE PLASMID ENHANCES SALMONELLA-INDUCED LYSIS OFMACROPHAGES AND INFLUENCES INFLAMMATORY RESPONSES

The Salmonella dublin virulence plasmid mediates systemic infection in mice and cattle. Here, we analyze the interaction between wild-type a nd plasmid-cured Salmonella strains with phagocytes in vitro and in vi vo. The intracellular recovery of S. dublin from murine peritoneal and bovine alveolar macrophages cultured in the presence of gentamicin in vitro was not related to virulence plasmid carriage. However, the vir ulence plasmid increased the lytic activity of S. dublin, Salmonella t yphimurium, and Salmonella choleraesuis for resident or activated mous e peritoneal macrophages. Lysis was not mediated by spv genes and was abolished by cytochalasin D treatment. Peritoneal and splenic macropha ges were isolated from mice 4 days after intraperitoneal infection wit h wild-type or plasmid-cured S. dublin strains. The wild-type strain w as recovered in significantly higher numbers than the plasmid-cured st rain. However, the intracellular killing rates of such cells cultured in vitro for both S. dublin strains were not significantly different, Four days after infection, there was a lower increase of phagocyte num bers in the peritoneal cavities and spleens of mice infected,vith the wild-type strain compared with the plasmid-cured strain, The virulence plasmid influenced the survival of macrophages in vitro following inf ection in vivo as assessed by microscopy, Cells from mice infected wit h the plasmid-cured strain survived better than those from mice infect ed with the wild-type strain, This is the first report demonstrating a n effect of the virulence plasmid on the interaction of Salmonella str ains with macrophages. Plasmid-mediated macrophage dysfunction could i nfluence the recruitment and/or the activation of phagocytic cells and consequently the net growth of Salmonella strains during infection.