Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2
2013
Xu, Yanquan | Chen, Wenjun | Bian, Meng | Wang, Xiaoyun | Sun, Jiufeng | Sun, Hengchang | Jia, Feifei | Liang, Chi | Li, Xuerong | Zhou, Xiao-nong | Huang, Yan | Yu, Xinbing
BACKGROUND: Clonorchis sinensis (C. sinensis, Cs) is a trematode parasite that often causes chronic cumulative infections in the hepatobiliary ducts of the host and can lead to pathological changes by continuously released excretory/secretory proteins (ESPs). A T2 ribonuclease in trematode ESPs, has been identified as a potent regulator of dendritic cell (DCs) modulation. We wondered whether there was a counterpart present in Cs ESPs with similar activity. To gain a better understanding of Cs ESPs associated immune responses, we identified and characterized RNASET2 of C. sinensis (Cs RNASET2) in this paper. METHODS: We expressed Cs RNASET2 in Pichia pastoris and identified its molecular characteristics using bioinformatic analysis and experimental approaches. The immune modulation activities of Cs RNASET2 were confirmed by evaluating cytokine production and surface markers of recombinant Cs RNASET2 (rCs RNASET2) co-cultured DCs, and monitoring levels of IgG isotypes from rCs RNASET2 administered BALB/c mice. RESULTS: Cs RNASET2 appeared to be a glycoprotein of T2 ribonuclease family harboring conserved CAS motifs and rich in B-cell epitopes. Furthermore, Cs RNASET2 was present in Cs ESPs and was able to modulate cytokine production of DCs. In addition, rCs RNASET2 could significantly suppress the expression of lipopolysaccharide-induced DCs maturation markers. In addition, when subcutaneously administered with rCs RNASET2 there was a marked effect on IgG isotypes in mouse sera. CONCLUSION: Collectively, we revealed that Cs RNASET2, a T2 ribonuclease present in Cs ESPs, could modulate DCs maturation and might play an important role in C. sinensis associated immune regulation in the host.
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