Abstract
BackgroundHuman immunity to Schistosoma infection requires many years of exposure, and multiple infections and treatments to develop. Unlike humans, rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection. In macaques, schistosome egg production decreases after 8 weeks post-infection and by week 22, physiological impairment of the worm caused by unclarified antibody-mediated processes is observed. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques.MethodsWe used a microarray containing a large repertoire of glycoprotein- and glycolipid-derived glycans from different schistosome life stages to analyse anti-glycan serum IgG and IgM from S. japonicum-infected macaques during the course of infection and self-cure. We also used an in vitro schistosomula assay to investigate whether macaque sera containing anti-glycan antibodies can kill schistosomula.Conclusions/significanceAntibody responses towards schistosome glycans at week 4 post-infection were dominated by IgM while IgG was high at week 8. The profound increase in IgG was observed mainly for antibodies towards a large subset of glycans that contain (multi-)fucosylated terminal GalNAcβ1-4GlcNAc (LDN), and Galβ1-4(Fucα1–3)GlcNAc (LeX) motifs. In general, glycans with a higher degree of fucosylation gave rise to stronger antibody responses than non-fucosylated glycans. Interestingly, even though many IgG and IgM responses had declined by week 22 post-infection, IgG towards O-glycans with highly fucosylated LDN motifs remained. When incubating macaque serum with schistosomula in vitro, schistosomula death was positively correlated with the duration of infection of macaques; macaque serum taken 22 weeks post-infection caused most schistosomula to die, suggesting the presence of potentially protective antibodies. We hypothesize that IgGs against highly fucosylated LDN motifs that remain when the worms deteriorate are associated with infection clearance and the resistance to re-infection in macaques.
Highlights
Schistosomiasis is a debilitating parasitic disease caused by members of the helminth genus Schistosoma (S.), with S. mansoni, S. japonicum and S. haematobium being the most prevalent human species
To find out if anti-glycan responses could contribute to the natural clearance process, we followed the dynamics of anti-glycan serum antibodies in Schistosoma-infected macaques in a longitudinal study starting from the onset of infection until 22 weeks post-infection, when the macaques had eliminated most of the parasites
We found that sera of macaques taken after 22 weeks of infection contained high IgG titres towards specific schistosome glycan epitopes highly abundant on schistosome larvae
Summary
Schistosomiasis is a debilitating parasitic disease caused by members of the helminth genus Schistosoma (S.), with S. mansoni, S. japonicum and S. haematobium being the most prevalent human species. Praziquantel (PZQ) is widely used to treat human schistosomiasis by paralyzing adult worm muscles and damaging the tegument [3]. This exposes worm antigens to the host immune system [4] and leads to immune-mediated killing of the parasite. The immune responses triggered by degenerating worms can alter antibody and cytokine responses and provide short-term drug-induced resistance to re-infection [5, 6]. Since this resistance is short-lived, people in endemic areas still require repeated administration of PZQ [7]. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques.
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