The role of IFN-gamma in murine Salmonella typhimurium infection.

Influence of both recombinant interferon gamma (r-IFN-gamma) and monoclonal anti-IFN-gamma on murine Salmonella typhimurium infection was studied in vivo. As a challenge we used either a virulent or an avirulent strain of S. typhimurium. The avirulent strain is unable to replicate in the mouse spleen. The effect of IFN-gamma or anti-IFN-gamma treatment on infection was assayed by counting the number of bacteria in the spleens 1, 2, 4 or 7 days after infection. Exogenously supplied IFN-gamma was found to decrease the number of both the virulent and the avirulent bacteria in the spleens 1 day after challenge but thereafter had no detectable effect. Anti-IFN-gamma-treated mice were unable to clear a sub-lethal dose of the virulent bacteria. The enhanced growth of the bacteria in the spleen was seen after 2 days of infection. In the spleens of anti-IFN-gamma-treated mice and control mice the fate of the non-replicating bacteria was similar. We conclude that the mice produce IFN-gamma during the early phase of Salmonella infection and that this causes a reduction in the apparent growth rate of the virulent bacteria. Because the avirulent bacteria, which do not multiply, were not affected by anti-IFN-gamma treatment, the effect of IFN-gamma is primarily bacteriostatic rather than bactericidal. After challenge, the production of IFN-gamma seems to start with a lag of approximately 2 days.