Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E).
Trypanosoma cruzi causes a suppression of the immune system leading to persistence in host cells. The trans-sialidase expressed by T. cruzi is a major virulence factor and transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite. Here we demonstrate that these sialylated structures play a role in the immunosuppression. We used two T. cruzi strains, whose TS activity correlated with their pathogenicity. The Tulahuen strain, characterized by a high TS activity efficiently infected mice, whereas the Tehuantepec strain showing a reduced TS activity could not establish a patent parasitemia. In vitro analysis revealed that these two strains invaded phagocytic and non-phagocytic host cells at a comparable rate, but they exhibited different potentials to modulate dendritic cell function. In contrast to Tehuantepec, the Tulahuen strain suppressed the production of the proinflammatory cytokine IL-12 and subsequent T-cell activation. This inhibitory effect was absent upon desialylation of the parasite. Therefore, we analysed whether sialylated structures of T. cruzi interact with the inhibitory sialic acid-binding protein Siglec-E on DC. Indeed, Siglec-E interacted with the pathogenic Tulahuen strain, but showed a diminished binding to the Tehuantepec strain. Ligation of Siglec-E on DC using antibodies confirmed this inhibitory effect on DC function.
Erdmann
Hanna
H
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Steeg
Christiane
C
Koch-Nolte
Friedrich
F
Fleischer
Bernhard
B
Jacobs
Thomas
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012794:Sialic Acids / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D006023:Glycoproteins; D008024:Ligands; D008565:Membrane Proteins; D012794:Sialic Acids; C422908:Siglece protein, mouse; D037521:Virulence Factors; D018664:Interleukin-12; C069715:trans-sialidase; D009439:Neuraminidase