Immunoactive N-glycans found in the dog heartworm

The parasitic nematode Dirofilaria immitis primarily infects dogs, but also humans with its geographic range increasing due to climate change. Recently Katharina Paschinger and Iain Wilson published in Nature Communications that significant glycomic features of this nematode are immunoactive.

Climate change is not just about it getting hot, but it could make you ill - one reason is that mosquito and pathogen species not currently common in Northern and Central Europe will be able to extend their geographic range. One example is the parasitic, filarial worm Dirofilaria immitis which is spread by mosquitoes and infects primarily canine species (dogs) causing severe heart disease. Especially the change in host from dog to insect is obligatory for the larval development from L1 to the infective L3, which can then reinfect dogs. As resistance starts to occur for the existing medical treatment (which leaves heart surgery as the only possibility to remove the worms) and cases in humans have also been reported, prevention strategies including vaccination are considered.

Driven by the biomolecular potential of sugar residues that modify proteins (so called N-glycans), the molecular glycobiology group at the BOKU (Katharina Paschinger / Iain Wilson) started the challenging in depth analysis of the N-glycome of this nematode. Using liquid chromatography and mass spectrometry they were able to identify “known” immunmodulatory modifications such as phosphorylcholine, but also - for the first time in worms - glucuronic acid, an anionic modification. Analytical challenging were the high molecular weight N-glycans (up to 7000 Daltons) with up to four antennae.

The sugar modifications were also subject to immuno-functional studies with a newly established glycan microarray method (Barbara Eckmair / Shi Yan) studying the recognition of the immobilized native sugars with dog sera, lectins (proteins that bind sugars) and pentraxins (immunological response proteins which are indicative of inflammation).

The new results, published in Nature Communications and highlighted in the March edition of The VetJournal, suggest that the parasite´s native sugar modifications mediate immunomodulation of the host and offer them ability to avoid host immune surveillance.