Innate Activation of IFN-γ-iNOS Axis During Infection With Represses the Ability of T Cells to Produce IL-2.

Pathogenic serovars are a major cause of enteric illness in humans and animals, and produce clinical manifestations ranging from localized gastroenteritis to systemic disease. T cells are a critical component of immunity against this intracellular pathogen. The mechanisms by which modulates T-cell-mediated immune responses in order to establish systemic infection are not completely understood. We show that infection of mice with serovar Typhimurium (. Typhimurium) suppresses IL-2 and increases IFN-γ and IL-17 production from T cells activated or through the T cell receptor. Infection with . Typhimurium brings about recruitment of CD11bGr1 suppressor cells to the spleen. depletion of these cells restores the ability of activated T cells to produce IL-2 and brings secretion of IFN-γ and IL-17 from these cells back to basal levels. The reduction in IL-2 secretion is not seen in IFN-γ and iNOS mice infected with . Our findings demonstrate that sustained innate activated IFN-γ production during progression of infection with reduces IL-2-secreting capability of T cells through an iNOS-mediated signaling pathway that can adversely affect long term immunity against this pathogen.