Differential cytokine expression in avian cells in response to invasion by Salmonella typhimurium, Salmonella enteritidis and Salmonella gallinarum

Salmonella enterica is a facultative intracellular pathogen that is capable of causing disease in a range of hosts. Although human salmonellosis is frequently associated with consumption of contaminated poultry and eggs, and the serotypes Salmonella gallinarum and Salmonella pullorum are important world-wide pathogens of poultry, little is understood of the mechanisms of pathogenesis of Salmonella in the chicken. Type III secretion systems play a key role in host cell invasiveness and trigger the production of pro-inflammatory cytokines during invasion of mammalian hosts, This results in a polymorphonuclear cell influx that contributes to the resulting enteritis. In this study, a chicken primary cell culture model was used to investigate the cytokine responses to entry by the broad host range serotypes S. enteritidis and S typhimurium, and the host specific serotype S, gallinarum, which rarely causes disease outside its main host, the chicken. The cytokines interleukin (IL)-1 beta IL-2, IL-6 and interferon (IFN)-gamma were measured by quantitative RT-PCR, and production of IL-6 and IFN-gamma was also determined through bioassays. All serotypes were invasive and had little effect on the production of IFN-gamma compared with non-infected cells; S, enteritidis invasion caused a slight downregulation of IL-2 production. For IL-1 beta production, infection with S. typhimurium had little effect, whilst infection with S. gallinarum or S, enteritidis caused a reduction in IL-1 beta mRNA levels. Invasion of S typhimurium and S. enteritidis caused an eight- to tenfold increase in production of the proinflammatory cytokine IL-6, whilst invasion by S gallinarum caused no increase. These findings correlate with the pathogenesis of Salmonella in poultry. S, typhimurium and S enteritidis invasion produces a strong inflammatory response, that may limit the spread of Salmonella largely to the gut, whilst S gallinarum does not induce an inflammatory response and may not be limited by the immune system, leading to the severe systemic disease fowl typhoid.