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Interferon-γ- and glucocorticoid-mediated pathways synergize to enhance death of CD4+ CD8+ thymocytes during Salmonella enterica serovar Typhimurium infection.
- Source :
- Immunology; Apr2013, Vol. 138 Issue 4, p307-321, 15p, 1 Diagram, 8 Graphs
- Publication Year :
- 2013
-
Abstract
- Thymic atrophy is known to occur during infections; however, there is limited understanding of its causes and of the cross-talk between different pathways. This study investigates mechanisms involved in thymic atrophy during a model of oral infection by Salmonella enterica serovar Typhimurium ( S. typhimurium). Significant death of CD4<superscript>+</superscript> CD8<superscript>+</superscript> thymocytes, but not of single-positive thymocytes or peripheral lymphocytes, is observed at later stages during infection with live, but not heat-killed, bacteria. The death of CD4<superscript>+</superscript> CD8<superscript>+</superscript> thymocytes is Fas-independent as shown by infection studies with lpr mice. However, apoptosis occurs with lowering of mitochondrial potential and higher caspase-3 activity. The amounts of cortisol, a glucocorticoid, and interferon-γ (IFN-γ), an inflammatory cytokine, increase upon infection. To investigate the functional roles of these molecules, studies were performed using Ifnγ<superscript>−/−</superscript> mice together with RU486, a glucocorticoid receptor antagonist. Treatment of C57 BL/6 mice with RU486 does not affect colony-forming units ( CFU), amounts of IFN-γ and mouse survival; however, there is partial rescue in thymocyte death. Upon infection, Ifnγ<superscript>−/−</superscript> mice display higher CFU and lower survival but more surviving thymocytes are recovered. However, there is no difference in cortisol amounts in C57 BL/6 and Ifnγ<superscript>−/−</superscript> mice. Importantly, the number of CD4<superscript>+</superscript> CD8<superscript>+</superscript> thymocytes is significantly higher in Ifnγ<superscript>−/−</superscript> mice treated with RU486 along with lower caspase-3 activity and mitochondrial damage. Hence, endogenous glucocorticoid and IFN-γ-mediated pathways are parallel but synergize in an additive manner to induce death of CD4<superscript>+</superscript> CD8<superscript>+</superscript> thymocytes during S. typhimurium infection. The implications of this study for host responses during infection are discussed. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 138
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 86025784
- Full Text :
- https://doi.org/10.1111/imm.12047