Helminth infections still belong
to the most prevalent infections of humans and animals. During infection,
glycoconjugates and specially those, substituted with phosphocholine
(PC), play a central role. These epitopes are present on glycosphingolipids
and (glyco)proteins. We concentrate on nematodes and the two model
systems Ascaris suum, a pig parasitic nematode and the free living
nematode Caenorhabditis elegans.
We have structurally elucidated the most complex glycosphingolipid
structures of a nematode from the parasitic nematode Ascaris suum
reported so far. These investigations revealed new structural motifs
and reflected the enormous glycosylation potential of nematodes.
Furthermore, we could - for the first time – isolate and identify
a PC-modified protein from C. elegans. In the future, additional
PC-modified proteins will be isolated, characterized and identified
and the PC-modification should be localized and structurally elucidated.
Besides the structural analyses, investigations on the biological
activities of these antigens are a major point of our interest.
PC-substituted antigens are known to have immunomodulatory activities.
Inhibition of lymphoid proliferation and induction of various cytokines
were observed. These investigations should continue and cellular
receptors of the PC-epitopes should be identified with an established
photo affinity labelling method.
The biosynthesis of non-host derived structures is a promising target
for the development of new anthelminthics. Several inhibitors of
the choline-metabolism and glycosphingolipid biosynthesis have already
revealed significant effects on the development of nematodes. To
elucidate additional inhibitors, the enzymes involved in the biosynthesis
of PC-epitopes should be identified by RNA interference experiments.