Abstract
Filariases are diseases caused by infection with filarial nematodes and transmitted by insect vectors. The filarial roundworm Dirofilaria immitis causes heartworm disease in dogs and other carnivores. D. immitis is closely related to Onchocerca volvulus, Wuchereria bancrofti and Brugia malayi, which cause onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) in humans and are neglected tropical diseases. Serum N-glycosylation is very sensitive to both pathological infections and changes in mammalian biology due to normal aging or lifestyle choices. Here, we report significant changes in the serum N-glycosylation profiles of dogs infected with D. immitis. Our data derive from analysis of serum from dogs with established patent infections and from a longitudinal infection study. Overall, galactosylation and core fucosylation increase, while sialylation decreases in infected dog sera. We also identify individual glycan structures that change significantly in their relative abundance during infection. Notably, the abundance of the most dominant N-glycan in canine serum (biantennary, disialylated A2G2S2) decreases by over 10 percentage points during the first 6 months of infection in each dog analyzed. This is the first longitudinal study linking changes in mammalian serum N-glycome to progression of a parasitic infection.
Highlights
Dirofilaria immitis is a filarial roundworm of considerable veterinary importance as the causative agent of heartworm disease in domestic dogs (Canis lupus familiaris) and cats (Felis silvestris catus)
We propose that individual glycan peaks in canine serum N-glycan profiles as well as more global markers, such as the relative abundance of sialylated glycans, could potentially be considered as glycobiomarker candidates for D. immitis infection in dogs
It is noteworthy that D. immitis is closely related to O. volvulus, W. bancrofti and B. malayi, causative agents of onchocerciasis and lymphatic filariasis afflicting more than 135 million humans[33,34], making our results relevant for a wider filariasis research community
Summary
Dirofilaria immitis is a filarial roundworm of considerable veterinary importance as the causative agent of heartworm disease in domestic dogs (Canis lupus familiaris) and cats (Felis silvestris catus). Glycan structure can be modulated due to changes in gene expression patterns that occur in response to environmental changes These changes in glycosylation range from fine-tuning biological processes to crucial contributions that enable novel biological functions[12]. We show the impact of parasitic infection with D. immitis on the total canine serum N-glycosylation profile. We observe remarkable changes in the abundances of core fucosylated, galactosylated and sialylated serum N-glycans when comparing healthy dogs to those that have established patent D. immitis infections. We propose that individual glycan peaks in canine serum N-glycan profiles as well as more global markers, such as the relative abundance of sialylated glycans, could potentially be considered as glycobiomarker candidates for D. immitis infection in dogs. While alterations in IgG N-glycosylation have previously been associated with leishmaniasis[35], asymptomatic filariasis[36] and other parasitic infection in developing countries[37] to the best of our knowledge, this is the first report of drastic changes in the mammalian total serum N-glycosylation profile as a consequence of parasitic infections
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