Susceptibility to Salmonella typhimurium infection and effectiveness of vaccination in mice deficient in the tumor necrosis factor alpha p55 receptor

Abstract

Mice defective in the ability to produce the tumor necrosis factor alpha p55 receptor (TNFαp55R) were orally challenged with a number of Salmonella typhimurium HWSH derivatives that differ in virulence. In comparison to TNFαp55R(+/+) mice, TNFαp55R(-/-) mice succumbed earlier to challenge with wild-type S. typhimurium HWSH and S. typhimurium HWSH purE. In contrast, TNFαp55R(-/-) mice were able to control an S. typhimurium HWSH aroA challenge, although greater numbers of Salmonella organisms were present in the tissues for a longer time period than was observed with TNFαp55R(+/+) mice. Vaccination of normal and TNFαp55R knockout animals with S. typhimurium HWSH aroA showed that TNFαp55R(-/-) mice, unlike TNFαp55R(+/+) mice, were not protected against a virulent S. typhimurium HWSH challenge. Splenocytes from TNFαp55R(-/-) mice exhibited a reduced ability to proliferate in the presence of S. typhimurium antigen compared to TNFαp55R(+/+) mice. Thus, TNFαp55R is essential for controlling Salmonella growth in tissues and for recall of immunity in murine salmonellosis.