Innate Activation of IFN-γ—iNOS Axis During Infection With Salmonella Represses the Ability of T Cells to Produce IL-2
| Autor: | Jitender Yadav, Neha Dikshit, Sana Ismaeel, Ayub Qadri |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1664-3224 37228447 |
| DOI: | 10.3389/fimmu.2020.00514 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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