Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus

Hewitson, J. P., Nguyen, D. L., van Diepen, A., Smit, C. H., Koeleman, C. A., McSorley, H. J., Murray, J., Maizels, R. M. and Hokke, C. H. (2016) Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. International Journal for Parasitology, 46(3), pp. 157-170. (doi: 10.1016/j.ijpara.2015.10.004) (PMID:26688390) (PMCID:PMC4776704)

Abstract

Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory–secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. We used MALDI-TOF-MS and LC–MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory–secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1–4GlcNAc) structure, respectively. We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory–secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory–secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory–secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host.

• Item Type: Articles
• Additional Information: The authors thank the Wellcome Trust, UK (Ref. 090281) and the American Asthma Foundation (Ref. 10-0234) for grant funding and the Core H of the Consortium for Functional Glycomics (Emory University School of Medicine, Atlanta, Georgia USA), funded by the National Institute of General Medical Sciences and the National Institutes of Health (USA) (GM62116 and P41GM103694) for generously performing the synthetic glycan array screening.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Hewitson, J. P., Nguyen, D. L., van Diepen, A., Smit, C. H., Koeleman, C. A., McSorley, H. J., Murray, J., Maizels, R. M., and Hokke, C. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Journal for Parasitology
• Publisher: Elsevier
• ISSN: 0020-7519
• Published Online: 12 December 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in International Journal for Parasitology 46(3): 157-170
• Publisher Policy: Reproduced under a Creative Commons License