The Trypanosoma cruzi trans-sialidase, through its COOH-terminal tandem repeat, upregulates interleukin 6 secretion in normal human intestinal microvascular endothelial cells and peripheral blood mononuclear cells

The Trypanosoma cruzi trans-sialidase can sensitize mice to become highly s usceptible to T. cruzi invasion, through mechanisms that remain unknown. In pursuing this observation, we found that purified trans-sialidase induces the selective release of biologically active interleukin (IL)-6 in naive hu man intestinal microvascular endothelial cells (HIMECs), peripheral blood m ononuclear cells (PBMCs), and bladder carcinoma cells. The trans-sialidase action was independent of its catalytic activity, as demonstrated with a ge netically engineered trans-sialidase mutant, an enzymatically active polype ptide, and cocultures of PBMCs with epimastigotes and trypomastigotes. Inst ead, the trans-sialidase action was reproduced with a recombinant COOH-term inal tandem repeat and with synthetic peptides modeled on the tandem repeat . Most interesting, HIMECs infected with a trypomastigote population expres sing trans-sialidase effectively released IL-6, but did not upon infection with the counterpart trypomastigote population expressing low trans-sialida se levels. IL-6 is a key factor in the regulation and symptom formation of infection caused by several types of viruses, such as HIV and influenza A v irus. However, the function of IL-6 in protozoan and other parasitic diseas es remains unclear. The unique findings presented here suggest that trans-s ialidase is a major inducer of IL-6 secretion in T. cruzi infection, indepe ndently of immune cell activation. Such IL-6 secretion might underlie some features of Chagas's disease, such as pyrexia, neuroprotection, and fibrosi s, and might result ill the undermining of normal acquired immunity against T. cruzi.