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

被引:44
作者
Saavedra, E
Herrera, M
Gao, W
Uemura, H
Pereira, MA
机构
[1] Tufts Univ, Sch Med, Parasitol Res Ctr, Dept Pathol, Boston, MA 02111 USA
[2] Nagasaki Univ, Inst Trop Med, Nagasaki 8528523, Japan
关键词
interleukin; 6; trans-sialidase; cytokines; Trypanosoma cruzi; endothelial cells;
D O I
10.1084/jem.190.12.1825
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 ill the undermining of normal acquired immunity against T. cruzi.
引用
收藏
页码:1825 / 1836
页数:12
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