Document Detail

Interferon-γ- and glucocorticoid-mediated pathways synergize to enhance death of CD4(+) CD8(+) thymocytes during Salmonella enterica serovar Typhimurium infection.
MedLine Citation:
PMID:  23186527     Owner:  NLM     Status:  MEDLINE    
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-γ (IFN-γ), an inflammatory cytokine, increase upon infection. To investigate the functional roles of these molecules, studies were performed using Ifnγ(-/-) 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-γ and mouse survival; however, there is partial rescue in thymocyte death. Upon infection, Ifnγ(-/-) 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 Ifnγ(-/-) mice. Importantly, the number of CD4(+) CD8(+) thymocytes is significantly higher in Ifnγ(-/-) 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(+) CD8(+) thymocytes during S. typhimurium infection. The implications of this study for host responses during infection are discussed.
Mukta Deobagkar-Lele; Suni K Chacko; Emmanuel S Victor; Jayachandra C Kadthur; Dipankar Nandi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  138     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-13     Completed Date:  2013-04-26     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  307-21     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
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MeSH Terms
Antigens, CD4 / genetics,  immunology
Antigens, CD8 / genetics,  immunology
Caspase 3 / genetics,  immunology
Cell Count
Cell Death / drug effects,  immunology
Gene Expression Regulation / drug effects
Hormone Antagonists / pharmacology
Hydrocortisone / biosynthesis,  immunology*
Interferon-gamma / biosynthesis,  genetics,  immunology*
Mice, Knockout
Mifepristone / pharmacology
Receptors, Glucocorticoid / antagonists & inhibitors
Salmonella Infections, Animal / immunology*,  microbiology,  mortality
Salmonella typhimurium / immunology*
Signal Transduction / drug effects
Stem Cells
Survival Rate
Thymocytes / immunology*,  microbiology,  pathology
Thymus Gland / immunology*,  microbiology,  pathology
Reg. No./Substance:
0/Antigens, CD4; 0/Antigens, CD8; 0/Hormone Antagonists; 0/Receptors, Glucocorticoid; 320T6RNW1F/Mifepristone; 82115-62-6/Interferon-gamma; EC 3.4.22.-/Caspase 3; WI4X0X7BPJ/Hydrocortisone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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