Differential production of interleukin-12 mRNA by murine macrophages in response to viable or killed Salmonella spp.

The use of attenuated Salmonella spp. as live oral vaccines and as vaccine carriers for foreign antigens has been extensively studied. We have shown that appropriately prepared nonviable organisms are as effective as viable organisms in eliciting humoral immune responses against a foreign antigen delivered by these vectors. It is not clear how strain viability affects the development of a cell-mediated immune response. In the present study, we demonstrate that BALB/c mice orally immunized with viable attenuated Salmonella spp. were protected against subsequent challenge while animals immunized with killed organisms were not. Protection was correlated with increased production of interleukin-12 (IL-12) p40 mRNA in the Peyer's patches within hours of oral administration. Peritoneal macrophages from lipopolysaccharide (LPS)-responsive and LPS-unresponsive mice mere also examined for production of IL-12 p40 mRNA following exposure to the viable or killed attenuated Salmonella carrier. There was dramatic upregulation of IL-12 p40 mRNA following exposure of macrophages to either viable or killed organisms. By 4 h postexposure, viable organisms had induced a 27-fold increase in IL-12 p40 mRNA levels while killed organisms had induced a 9-fold increase in IL-12 p40 mRNA levels. This was observed in macrophages isolated from both LPS-responsive and unresponsive mice. The higher levels of IL-12 induced by viable Salmonella spp. may result in the development of a Th1 response and cell-mediated immunity, while the lower levels of IL-12 induced by killed Salmonella spp. may not be sufficient to promote a Th1 response.