Trypanosoma cruzi infection suppresses nuclear factors that bind to specific sites on the interleukin-2 enhancer.
Interleukin-2 (IL-2) gene expression, a critical early event during T lymphocyte activation, is severely suppressed in mice infected with the protozoan parasite Trypanosoma cruzi, the causative agent of human Chagas' disease. Our previous observation that reduction of IL-2 mRNA in T cells from T. cruzi-infected mice is not due to an increased degradation of the mRNA suggests a repression of the IL-2 gene at the transcriptional level. In this study, we have measured the level of nuclear factors that bind to specific sites on the IL-2 enhancer. Splenocytes and splenic T cells from acutely infected mice show a marked decrease in the level of AP-1, and a modest decrease in the level of NF-kappa B and nuclear factor of activated T cells (NF-AT). DNA-binding activity of Oct-1 was least affected in T cells from infected mice. Although the basal level of AP-1 activity is comparable in cells from uninfected and infected mice, mitogen-induced AP-1 activation is absent in the cells from T. cruzi-infected mice. Sodium deoxycholate treatment slightly enhances NF-kappa B-binding activity in splenocyte nuclear and whole-cell extracts from infected mice, suggesting that a blockage of the activation of NF-kappa B is only partially responsible for the decrease in the level of NF-kappa B in T cells from T. cruzi-infected mice. These data identify the molecular basis of IL-2 gene regulation in T. cruzi infection and suggest that T cells are anergized as a result of the infection.
Department of Zoology, University of Georgia, Athens 30602.
L
L
Soong
R L
RL
Tarleton
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D014355:Chagas Disease / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors