| First Author | Deobagkar-Lele M | Year | 2013 |
| Journal | Immunology | Volume | 138 |
| Issue | 4 | Pages | 307-21 |
| PubMed ID | 23186527 | Mgi Jnum | J:198088 |
| Mgi Id | MGI:5495377 | Doi | 10.1111/imm.12047 |
| Citation | Deobagkar-Lele M, et al. (2013) Interferon-gamma- and glucocorticoid-mediated pathways synergize to enhance death of CD4(+) CD8(+) thymocytes during Salmonella enterica serovar Typhimurium infection. Immunology 138(4):307-21 |
| abstractText | 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(+) CD8(+) 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(+) CD8(+) 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-gamma (IFN-gamma), an inflammatory cytokine, increase upon infection. To investigate the functional roles of these molecules, studies were performed using Ifngamma(-/-) mice together with RU486, a glucocorticoid receptor antagonist. Treatment of C57BL/6 mice with RU486 does not affect colony-forming units (CFU), amounts of IFN-gamma and mouse survival; however, there is partial rescue in thymocyte death. Upon infection, Ifngamma(-/-) mice display higher CFU and lower survival but more surviving thymocytes are recovered. However, there is no difference in cortisol amounts in C57BL/6 and Ifngamma(-/-) mice. Importantly, the number of CD4(+) CD8(+) thymocytes is significantly higher in Ifngamma(-/-) mice treated with RU486 along with lower caspase-3 activity and mitochondrial damage. Hence, endogenous glucocorticoid and IFN-gamma-mediated pathways are parallel but synergize in an additive manner to induce death of CD4(+) CD8(+) thymocytes during S. typhimurium infection. The implications of this study for host responses during infection are discussed. |
