4.26 Glycoconjugates of Parasitic Helminth Infections R. D. Dennis, H. Geyer, and R. Geyer, University of Giessen, Giessen, Germany ß 2007 Elsevier Ltd. All rights reserved. 4.26.1 Introduction
4.26.2 Structural Modifications of Helminth Glycosylated Antigens
Why Schistosoma spp. eggs are a special case
220.127.116.11 Nematodes 18.104.22.168.1
Caenorhabditis elegans: A parasitic nematode model
4.26.3 Immunomodulatory Properties of Modified Helminth Glycosylated Antigens
4.26.1 Introduction In the past 50 years, there has been remarkably little change in the worldwide incidence of human, parasitic worm infections, in respect to the major gastrointestinal nematodes Ascaris lumbricoides, Trichuris trichiura, as well as the hookworms Ancylostoma duodenale and Necator americanus.1 Because of the intensive use of anthelminthics in the treatment of human and veterinary parasitic helminth diseases, there is a rule of thumb that emergence of resistance occurs within 10 years of introduction.2 Therefore, there is a continuous and urgent need for the development of new drugs with novel mechanisms of action. Such an example is the investigation of inhibitors that interfere with the pathways of nematode glycosphingolipid (GSL) biosynthesis and/or choline metabolism.3 What is(are) the underlying reason(s) for the pre-eminence of such metazoan parasites in terms of survival, longevity, growth, and reproduction? The ‘secret’ would appear to be immunomodulation, the ability on infection to generate a conducive, anti-inflammatory immune response dominated by a T-helper 2 (TH2) phenotype.4–7 Parasitic helminth-derived, protein-and/or lipid-bound antigenic glycans have been implicated in this phenomenon from the three major groups of helminth parasites: the cestodes (tapeworms),8 the trematodes (flukes),9 and the nematodes (roundworms).10 It will be the aim of this chapter to characterize the range of glycoconjugate structural elements synthesized by the various parasites and to analyze those involved, directly or indirectly, in the immunoregulation of the host’s immune response following infection.
4.26.2 Structural Modifications of Helminth Glycosylated Antigens Just a brief word is necessary to nomenclature of helminth glycoconjugates (as comprehensively summarized by Dell et al.).11 The oligosaccharide backbones of GSLs are defined in terms of ‘core series’ consisting of specific monosaccharide sequences, linkages, and anomeric configurations. Glycoproteins are of the N- and O-linked glycan types. O-glycans, with nonreducing terminals corresponding to N-glycans, are O-linked to serine/threonine via characteristic cores, the most frequent of which are core-1 type (Galb3GalNAca-) and core-2 type (GlcNAcb6[Galb3]GalNAca-). N-Glycans are defined by four classes of core types, namely, high mannose (Man5–9GlcNAc2), truncated (Man1–4GlcNAc2), complex (XMan3GlcNAc2), and hybrid (XMan4–5GlcNAc2; X corresponding to the various terminal and side chain ‘capping’ modifications as detailed in the next paragraph).