Abstracts (complete list) - Wissenschaft Online

Hanna Erdmann, Paul Crocker, Bernhard Fleischer, Thomas Jacobs
Pathogenic Trypanosoma cruzi interacts with the immune
modulatory molecule mouse Siglec-E (sialic acid-binding Iglike
lectin-E)
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a
chronic infection, in which a strong suppression of the immune response leads to a lifelong
persistence of parasites in host cells. The trypanosomal trans-sialidase is described
to be a major virulence factor. This enzyme allows the parasite to acquire sialic acids
from its environment by cleavage from host glycoconjugates and direct transfer to GPIanchored
mucin-like molecules on its own cell surface. In the current investigation we
provide evidence that the murine molecule Siglec-E directly interacts with sialylated
ligands on the surface of T. cruzi. Siglecs are sialic acid-binding Ig-like lectins that are
expressed on most cell types of the immune system. They have been shown to act as
inhibitory receptors, ascribed to the presence of conserved immunoreceptor tyrosinebased
inhibition motifs (ITIMs) in their cytoplasmic regions. The murine Siglec-E is
expressed on phagocytic cells as well as on NK cells. Using Siglec-E transfected CHOcells
and a Siglec-E-Fc fusion molecule we demonstrate that Siglec-E binds with high
affinity to both extracellular trypomastigotic and intracellular amastigotic parasites of
the pathogenic T. cruzi Tulahuen strain. In contrast, we can detect only a weak binding
of Siglec-E to extracellular trypomastigotic parasites of the apathogenic T. cruzi
Tehuantepec strain, whereas the binding of Siglec-E to intracellular amastigotic
parasites of this apathogenic strain is completely absent.
These results raise the possibility that the pathogenic parasite dampens immune
responses via binding to the inhibitory receptor Siglec-E, allowing the parasite to persist
and to establish a chronic infection.