The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1825/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 12, December 20, 1999 1825-1836

Original Article

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

Emma Saavedraa, Macario Herreraa, Wenda Gaoa, Haruki Uemurab, and Miercio A. Pereiraa
a Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111
b Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan

Correspondence to: Miercio A. Pereira, Department of Pathology, Parasitology Research Center, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Tel:617-636-2933 Fax:617-636-6849 E-mail:maperrin{at}yahoo.com.

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.

Key Words: interleukin 6, trans-sialidase, cytokines, Trypanosoma cruzi, endothelial cells


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