Changes in canine serum N-glycosylation as a result of infection with the heartworm parasite Dirofilaria immitis

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.

Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi

“…4). When focusing on broad classes of glycans, we noted an overall increase of galactosylation and a reduction in sialylation that were similarly reported for D. immitis infections [51]. Interestingly, although higher degrees of fucosylation have previously been associated with various disease conditions [71][72][73] -including during infection with D. immitis [51] -we could not observe any clear and statistically signi cant trend regarding changes in the abundance of fucosylation during primate infection with B. malayi (Fig.…”

“…Here, we de ned the healthy macaque serum N-glycopro le and used it as a baseline to study the changes in N-glycosylation during establishment of infection with the parasitic larial nematode B. malayi. This longitudinal serum set did not yield striking visual changes within the serum N-glycan pro les such as those that have been observed in infection with the larial nematode D. immitis in dogs [51]. Nonetheless, we highlighted many statistically signi cant changes between the various post infection time-points and the stable baseline de ned by the uninfected pro le (Fig.…”

“…Finally, taking advantage of the use of the exact same work ow for both studies, we compared the changes observed in rhesus macaque N-glycans during infection with B. malayi with the changes in canine serum N-glycans during infection with the dog heartworm Diro laria immitis (D. immitis) [51]. We compared the alteration of serum N-glycosylation observed at 27 wpi for the dogs and at 15 wpi for the rhesus macaques since these time-points coincide with the micro lariaemic stage of infection for the animals in both studies.…”

“…Statistical analysis was performed using the software R (version 4.0.0 Patched). The MSstats package[62] (10.18129/B9.bioc.MSstats) was used to assess signi cant changes between time-points in the course of disease progression as described previously [51].…”

Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi

“…Rhesus macaques, in particular have shown high similarities with humans in terms of lymphatic pathology and immune responses 38 , 39 . However, application of serum or IgG glycoprofiling for infectious diseases has focused mostly on infection with viral or bacterial pathogens 22 , 47 with very few studies addressing infections with eukaryotic parasites such as protozoa 48 – 50 or metazoan flatworms and nematodes 48 , 51 , 52 .…”