Yang Y Y Michelle, Li Xiao Hong, Brzezicka Katarzyna, Reichardt Niels-Christian, Wilson R Alan, van Diepen Angela, Hokke Cornelis H
Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, and Key Laboratory of Parasitology and Vector Biology, Ministry of Health, Shanghai, China.
PLoS Negl Trop Dis. 2017 Feb 2;11(2):e0005339. doi: 10.1371/journal.pntd.0005339. eCollection 2017 Feb.
Human 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.
We 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/SIGNIFICANCE: Antibody 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.
人类对血吸虫感染的免疫力需要多年的接触、多次感染和治疗才能形成。与人类不同，恒河猴能自然清除已建立的血吸虫感染，同时获得对再感染的免疫力。在猕猴中，感染后8周血吸虫卵产量下降，到第22周时，观察到由不明抗体介导的过程导致蠕虫出现生理损伤。由于在人类和动物感染中均观察到针对血吸虫聚糖抗原的强烈抗体反应，因此我们在此研究抗聚糖抗体是否与猕猴对血吸虫感染的免疫力相关。
我们使用了一种微阵列，其中包含来自不同血吸虫生活阶段的大量糖蛋白和糖脂衍生聚糖，以分析日本血吸虫感染猕猴在感染和自愈过程中血清中的抗聚糖IgG和IgM。我们还使用体外尾蚴试验来研究含有抗聚糖抗体的猕猴血清是否能杀死尾蚴。
结论/意义：感染后第4周，针对血吸虫聚糖的抗体反应以IgM为主，而第8周时IgG水平较高。IgG的显著增加主要见于针对一大类含有（多）岩藻糖基化末端GalNAcβ1-4GlcNAc（LDN）和Galβ1-4（Fucα1-3）GlcNAc（LeX）基序的聚糖的抗体。一般来说，岩藻糖基化程度较高的聚糖比非岩藻糖基化聚糖引发更强的抗体反应。有趣的是，尽管感染后第22周时许多IgG和IgM反应已经下降，但针对具有高度岩藻糖基化LDN基序的O-聚糖的IgG仍然存在。当在体外将猕猴血清与尾蚴一起孵育时，尾蚴死亡与猕猴的感染持续时间呈正相关；感染后22周采集的猕猴血清导致大多数尾蚴死亡，表明存在潜在的保护性抗体。我们推测，在蠕虫退化时仍存在的针对高度岩藻糖基化LDN基序的IgG与猕猴感染清除和对再感染的抵抗力有关。
