AUTHOR=Yadav Jitender , Dikshit Neha , Ismaeel Sana , Qadri Ayub TITLE=Innate Activation of IFN-γ—iNOS Axis During Infection With Salmonella Represses the Ability of T Cells to Produce IL-2 JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00514 DOI=10.3389/fimmu.2020.00514 ISSN=1664-3224 ABSTRACT=

Pathogenic Salmonella 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 Salmonella modulates T-cell—mediated immune responses in order to establish systemic infection are not completely understood. We show that infection of mice with Salmonella enterica serovar Typhimurium (S. Typhimurium) suppresses IL-2 and increases IFN-γ and IL-17 production from T cells activated in vivo or ex vivo through the T cell receptor. Infection with S. Typhimurium brings about recruitment of CD11b⁺Gr1⁺ suppressor cells to the spleen. Ex vivo 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 Salmonella. Our findings demonstrate that sustained innate activated IFN-γ production during progression of infection with Salmonella reduces IL-2—secreting capability of T cells through an iNOS-mediated signaling pathway that can adversely affect long term immunity against this pathogen.