Highly modified and immunoactive N-glycans of the canine heartworm

Nat Commun. 2019 Jan 8;10(1):75. doi: 10.1038/s41467-018-07948-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein / immunology
  • C-Reactive Protein / metabolism
  • Chromatography, High Pressure Liquid / methods
  • Complement C1q / immunology
  • Complement C1q / metabolism
  • Dirofilaria immitis / chemistry
  • Dirofilaria immitis / immunology*
  • Dirofilariasis / immunology*
  • Dirofilariasis / parasitology
  • Dogs
  • Female
  • Glycomics / methods*
  • Glycosylation
  • Host-Parasite Interactions / immunology*
  • Immunologic Surveillance / immunology
  • Male
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Polysaccharides / metabolism
  • Protein Binding
  • Tandem Mass Spectrometry / methods

Substances

  • Polysaccharides
  • Complement C1q
  • C-Reactive Protein