Trypanosoma cruzi infection suppresses nuclear factors that bind to specific sites on the interleukin

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Abstract
Interleukin‐2 (II‐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‐xB 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‐xB‐binding activity in splenocyte nuclear and whole‐cell extracts from infected mice, suggesting that a blockage of the activation of NF‐xB is only partially responsible for the decrease in the level of NF‐xB 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.