Highly modified and immunoactive N-glycans of the canine heartworm

• Published in: Nature communications 2019-01, Vol.10 (1), p.75-18, Article 75
• Main Authors: Martini, Francesca, Eckmair, Barbara, Štefanić, Saša, Jin, Chunsheng, Garg, Monika, Yan, Shi, Jiménez-Castells, Carmen, Hykollari, Alba, Neupert, Christine, Venco, Luigi, Varón Silva, Daniel, Wilson, Iain B. H., Paschinger, Katharina
• Format: Article
• Language: English
• Subjects: 101/58; 1988; 49/61; 631/326/417/2546; 631/45/1268; 631/45/221; 631/45/72/1202; Animals; Aquatic insects; ates of america; C-reactive protein; C-Reactive Protein - immunology; C-Reactive Protein - metabolism; Chromatography, High Pressure Liquid - methods; Climate change; Complement C1q - immunology; Complement C1q - metabolism; Complement component C1q; Dimensional analysis; Dimensional changes; Dirofilaria immitis - chemistry; Dirofilaria immitis - immunology; dirofilaria-immitis; Dirofilariasis - immunology; Dirofilariasis - parasitology; Dogs; experimental parasitology; Female; Fucose; Glycan; Glycomics - methods; Glycosylation; helminths; High-performance liquid chromatography; Host-Parasite Interactions - immunology; Humanities and Social Sciences; Immunoglobulin M; Immunologic Surveillance - immunology; Immunomodulation; Immunosurveillance; important epitope; Infectious Medicine; Infektionsmedicin; linked; Liquid chromatography; Male; Mannose; Mathematical analysis; multidisciplinary; N-glycans; Nematodes; o-glycans; oligosaccharides; Organic chemistry; otocols; ott al; p167; p307; parasitic; Parasitics (electronics); pe2209; Phosphorylcholine; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - immunology; Polysaccharides - metabolism; protective immunity; Protein Binding; Proteins; schistosoma-mansoni; Science; Science & Technology - Other Topics; Science (multidisciplinary); symbol nomenclature; Tandem Mass Spectrometry - methods; v110; v1503; v67
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07948-7

The canine heartworm ( Dirofilaria immitis ) is a mosquito-borne parasitic nematode whose range is extending due to climate change. In a four-dimensional analysis involving HPLC, MALDI-TOF–MS and MS/MS in combination with chemical and enzymatic digestions, we here reveal an N-glycome of unprecedented complexity. We detect N-glycans of up to 7000 Da, which contain long fucosylated HexNAc-based repeats, as well as glucuronylated structures. While some modifications including LacdiNAc, chitobiose, α1,3-fucose and phosphorylcholine are familiar, anionic N-glycans have previously not been reported in nematodes. Glycan array data show that the neutral glycans are preferentially recognised by IgM in dog sera or by mannose binding lectin when antennal fucose and phosphorylcholine residues are removed; this pattern of reactivity is reversed for mammalian C-reactive protein, which can in turn be bound by the complement component C1q. Thereby, the N-glycans of D. immitis contain features which may either mediate immunomodulation of the host or confer the ability to avoid immune surveillance. The glycome of parasites can have immunomodulatory properties or help to avoid immune surveillance, but details are unknown. Here, Martini et al. characterize the N-glycome of the canine heartworm, reveal an unprecedented complexity, particularly in anionic N-glycans, and determine recognition by components of the immune system.