DIFFERENTIAL PRODUCTION OF INTERLEUKIN-12 MESSENGER-RNA BY MURINE MACROPHAGES IN RESPONSE TO VIABLE OR KILLED SALMONELLA SPP

The use of attenuated Salmonella spp. as live oral vaccines and as vac cine carriers for foreign antigens has been extensively studied. We ha ve shown that appropriately prepared nonviable organisms are as effect ive as viable organisms in eliciting humoral immune responses against a foreign antigen delivered by these vectors. It is not clear how stra in viability affects the development of a cell-mediated immune respons e. In the present study, we demonstrate that BALB/c mice orally immuni zed with viable attenuated Salmonella spp. were protected against subs equent challenge while animals immunized with killed organisms were no t. Protection was correlated with increased production of interleukin- 12 (IL-12) p40 mRNA in the Peyer's patches within hours of oral admini stration. Peritoneal macrophages from lipopolysaccharide (LPS)-respons ive and LPS-unresponsive mice mere also examined for production of IL- 12 p40 mRNA following exposure to the viable or killed attenuated Salm onella carrier. There was dramatic upregulation of IL-12 p40 mRNA foll owing 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 incr ease in IL-12 p40 mRNA levels. This was observed in macrophages isolat ed from both LPS-responsive and unresponsive mice. The higher levels o f IL-12 induced by viable Salmonella spp. may result in the developmen t 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 p romote a Th1 response.