Salmonella infection does not increase expression and activity of the highaffinity IL-12 receptor

Expression of high affinity IL-12 receptors is required for IL-12-mediated IFN-gamma production. Activation of this pathway has been shown to be criti cal in generating optimal cell-mediated immunity, Therefore, increased IL-1 2 receptor expression might be expected in the host response after infectio n by an intracellular bacterial pathogen, In the present study, we have mad e the surprising discovery that infection with Salmonella results in an ear ly reduction of high aflinity IL-12 receptor expression and activation. Aft er oral inoculation with Salmonella, the level of mRNA expression encoding IL-12 receptor beta2 (IL-12R beta2) subunit was diminished 12 h postinfecti on in the mesenteric lymph nodes and subsequently in the spleen. Furthermor e, decreased IL-12R beta2 mRNA expression was observed in CD4(+) T lymphocy tes isolated from the mesenteric lymph nodes and spleens of infected mice. Attenuated IL-12R beta2 mRNA expression correlated with reduced receptor si gnaling, as demonstrated by reduced IL-12-induced STAT4 phosphorylation in enriched T lymphocytes isolated from the mesenteric lymph nodes and spleens of Salmonella-infected mice. These in vivo results were substantiated with an in vitro model system, In this model system, T lymphocytes cocultured w ith Salmonella-infected macrophages expressed less IL-12R beta2 mRNA. The c ocultured T cells were also less responsive to IL-12 as assessed by reduced phosphorylation of STAT4 and limited IFN-gamma secretion, Together, these studies suggest that Salmonella can limit an optimal host immune response b y reducing the expression and activity of high affinity IL-12 receptors.