Role of gamma interferon in late stages of murine salmonellosis.

Gamma interferon (IFN-gamma) is an important mediator of natural resistance of mice to Salmonella species during the first week of infection, when it restricts the rate of intracellular growth of the bacteria but does not lead to their killing (A. Muotiala and P. H. Mäkelä, Microb. Pathog. 8:135-141, 1990). We used the experimental mouse salmonellosis model to investigate the role of IFN-gamma in the later stages of a sublethal infection and the ensuing specific immunity. When anti-IFN-gamma was administered starting 6 days after challenge, it did not prevent the cessation of intracellular bacterial growth and the formation of the plateau stage in the second week of infection. In addition, anti-IFN-gamma given 14 and 16 days after challenge did not alter the elimination of the bacteria in the clearance stage in the third week of infection. When mice immunized 2 months previously with live vaccine were infected with virulent salmonellae, depletion of IFN-gamma enhanced the early growth of the bacteria in the same manner as that seen in naive mice. However, when the immunized mice were infected with attenuated aroA bacteria, their clearance started immediately and was unaffected by IFN-gamma depletion, demonstrating that IFN-gamma is not required for the clearance. We conclude that IFN-gamma restricts the rate of intracellular bacterial multiplication in the first week of Salmonella infection in both naive and immune mice but is not a mediator of bacterial clearance in either naive or immunized mice.