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The Trypanosoma cruzi trans-sialidase can sensitize mice to become highly susceptible 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 human intestinal microvascular endothelial cells (HIMECs), peripheral blood mononuclear cells (PBMCs), and bladder carcinoma cells. The trans-sialidase action was independent of its catalytic activity, as demonstrated with a genetically engineered trans-sialidase mutant, an enzymatically active polypeptide, and cocultures of PBMCs with epimastigotes and trypomastigotes. Instead, the trans-sialidase action was reproduced with a recombinant COOH-terminal tandem repeat and with synthetic peptides modeled on the tandem repeat. Most interesting, HIMECs infected with a trypomastigote population expressing trans-sialidase effectively released IL-6, but did not upon infection with the counterpart trypomastigote population expressing low trans-sialidase 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 virus. However, the function of IL-6 in protozoan and other parasitic diseases remains unclear. The unique findings presented here suggest that trans-sialidase is a major inducer of IL-6 secretion in T. cruzi infection, independently of immune cell activation. Such IL-6 secretion might underlie some features of Chagas's disease, such as pyrexia, neuroprotection, and fibrosis, and might result in the undermining of normal acquired immunity against T. cruzi.

the journal of experimental medicine/the journal of experimental medicine

The <i>Trypanosoma cruzi trans</i>-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, through Its Cooh-Terminal Tandem Repeat, Upregulates Interleukin 6 Secretion in Normal Human Intestinal Microvascular Endothelial Cells and Peripheral Blood Mononuclear Cells