Limited interleukin-18 response in Salmonella-infected murine macrophages and in Salmonella-infected mice

Optimal immune responses against an intracellular bacterial pathogen, such as Salmonella, involve the production of gamma interferon (IFN-gamma), whic h activates macrophages, It has recently been suggested that, interleukin-1 8 (IL-18), in addition to IL-12, contributes to the induction of IFN-gamma following infection. Given this hypothesis, an optimal host immune response against intracellular bacterial pathogens would include the induction of I L-18 secretion by macrophages due to Salmonella infection. We questioned wh ether Salmonella could induce macrophages to upregulate their expression of IL-18 mRNA and secretion of IL-18, With cultures of murine macrophages, we were surprised to find that infection by wild-type Salmonella dublin resul ted in decreased expression of IL-18 mRNA and IL-18 secretion rather than a n increase. Reduction of macrophage-derived IL-18 expression by wild-type S almonella occurred early in the response, suggesting a direct effect. Furth ermore, mice orally inoculated with wild-type Salmonella were shown to have reduced IL-18 mRNA expression at mucosal sites within hours postinoculatio n, Together these studies demonstrate Salmonella-induced reductions in IL-1 8 expression, suggesting that this intracellular pathogen may be capable of limiting a potentially protective immune response.