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 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.
Saavedra
E
E
Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Herrera
M
M
Gao
W
W
Uemura
H
H
Pereira
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000469:parasitology; D006023:Glycoproteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008833:Microcirculation; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D020080:Tandem Repeat Sequences; D015854:Up-Regulation / Q000187:drug effects
D006023:Glycoproteins; D015850:Interleukin-6; C069715:trans-sialidase; D009439:Neuraminidase