Effect of late administration of anti-TNα antibodies on a Salmonella infection in the mouse model

The effect of late administration of anti-TNFα antibodies on the course of a Salmonella infection in mice was evaluated. Administration of anti-TNFα antiserum as late as day 5 after challenge enhanced a sublethal primary infection with the virulent Salmonella typhimurium C5 in innately resistant (Ity^s) A/J mice by preventing the suppression of exponential bacterial growth in the reticuloendothelial system (RES) (plateau phase). When the anti-TNFα treatment was started well after the establishment of the plateau (day 7) a prompt relapse of the infection occurred, with the rapid resurgence of bacterial growth in the reticuloendothelial system leading to the death of the animals. In contrast, late administration of the antiserum did not affect the clearance from the tissues of an avirulent temperature-sensitive mutant of S. typhimurium C5 (C5TS). Innately susceptible (Ity^s) BALB/c mice immunized with the SL3261 aroA live vaccine acquire solid long-lasting protection from oral challenge with the virulent C5 strain, suppressing growth of the challenge in the RES. Administration of anti-TNFα antibodies on day 8 of a secondary oral infection with strain C5 abrogated vaccine induced protection, with a progressive increase of bacterial numbers in the RES leading to the death of the animals. The results indicate that TNFα is constantly required for the control of virulent salmonellae in the RES, both in a sublethal primary infection in innately resistant mice and also in a secondary infection in innately susceptible mice immunized with a live vaccine. TNFα may not be essential for bacterial clearance of avirulent organisms from the tissues.