Glycobiology Advance Access originally published online on September 11, 2009
Glycobiology 2010 20(1):2-12; doi:10.1093/glycob/cwp140
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Review |
Glycan gimmickry by parasitic helminths: A strategy for modulating the host immune response?
2 Department of Molecular Cell Biology & Immunology, VU University Center, Amsterdam, The Netherlands
3 Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia, USA
1 To whom correspondence should be addressed: Tel: +31-20-4448157; Fax: +31-20-4448081; e-mail: im.vandie{at}vumc.nl
Received on July 2, 2009; revised on September 1, 2009; accepted on September 3, 2009
Parasitic helminths (worms) co-evolved with vertebrate immune systems to enable long-term survival of worms in infected hosts. Among their survival strategies, worms use their glycans within glycoproteins and glycolipids, which are abundant on helminth surfaces and in their excretory/ secretory products, to regulate and suppress host immune responses. Many helminths express unusual and antigenic (nonhost-like) glycans, including those containing polyfucose, tyvelose, terminal GalNAc, phosphorylcholine, methyl groups, and sugars in unusual linkages. In addition, some glycan antigens are expressed that share structural features with those in their intermediate and vertebrate hosts (host-like glycans), including LeX (Galβ1-4[Fuc
1-3]GlcNAc-), LDNF (GalNAcβ1-4[Fuc1-3]GlcNAc-), LDN (GalNAcβ1-4GlcNAc-), and Tn (GalNAc1-O-Thr/Ser) antigens. The expression of host-like glycan determinants is remarkable and suggests that helminths may gain advantages by synthesizing such glycans. The expression of host-like glycans by parasites previously led to the concept of "molecular mimicry," in which molecules are either derived from the pathogen or acquired from the host to evade recognition by the host immune system. However, recent discoveries into the potential of host glycan-binding proteins (GBPs), such as C-type lectin receptors and galectins, to functionally interact with various host-like helminth glycans provide new insights. Host GBPs through their interactions with worm-derived glycans participate in shaping innate and adaptive immune responses upon infection. We thus propose an alternative concept termed "glycan gimmickry," which is defined as an active strategy of parasites to use their glycans to target GBPs within the host to promote their survival.
Key words: C-type lectins / helminth glycans / immune modulation / parasitic helminth