IkB and NF-kB in GM-CSF Antagonism of Dexamethasone Suppression of Macrophage Response to Aspergillus fumigatus conidia


Author address: 

Cal. Inst. for Med. Research, San Jose, CA.


Background: The immunosuppressive effect of dexamethasone (DEX) on macrophage killing activity and cytokine production in response to Aspergillus fumigatus conidia is antagonized by granulocyte-macrophage colonystimulating factor (GM-CSF). As steroids and GM-CSF utilize different receptors and signalling pathways, we investigated whether a locus of interaction for these opposing immunomodulators could be through IkB regulation of translocation of NF-kB. IkB binds NF-kB blocking translocation, whereas T27K for 5d followed by 30 min 10 ng/ml rhu IL-12 was 0.143 compared to 0.010 for cells from non-immune donors (p=0.002). Conclusion: These results demonstrate that the IL-12R/STAT-4 pathway is specifically activated by coccidioidal antigen in cells from immune donors. Because cells from anergic donors do not respond to IL-12, lack of activation of the IL-12R/STAT- 4 pathway may play a role in coccidioidal anergy.

abstract No: 


Full conference title: 

42nd Annual Meeting Infectious Diseases Society of America
    • Infectious Diseases Society of America 42nd