Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2

Abstract

BackgroundClonorchis 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 CsESPs with similar activity. To gain a better understanding of CsESPs associated immune responses, we identified and characterized RNASET2 of C. sinensis (CsRNASET2) in this paper.MethodsWe expressed CsRNASET2 in Pichia pastoris and identified its molecular characteristics using bioinformatic analysis and experimental approaches. The immune modulation activities of CsRNASET2 were confirmed by evaluating cytokine production and surface markers of recombinant CsRNASET2 (rCsRNASET2) co-cultured DCs, and monitoring levels of IgG isotypes from rCsRNASET2 administered BALB/c mice.ResultsCsRNASET2 appeared to be a glycoprotein of T2 ribonuclease family harboring conserved CAS motifs and rich in B-cell epitopes. Furthermore, CsRNASET2 was present in CsESPs and was able to modulate cytokine production of DCs. In addition, rCsRNASET2 could significantly suppress the expression of lipopolysaccharide-induced DCs maturation markers. In addition, when subcutaneously administered with rCsRNASET2 there was a marked effect on IgG isotypes in mouse sera.ConclusionCollectively, we revealed that CsRNASET2, a T2 ribonuclease present in CsESPs, could modulate DCs maturation and might play an important role in C. sinensis associated immune regulation in the host.

Haemonchus contortusexcretory and secretory proteins (HcESPs) suppress functions of goat PBMCsin vitro

“…Another cell line, T regulatory cells (TReg), and its typical cytokine IL-10 usually played suppressive functions in the immune responses. It inhibited the development of Th2 cell responses [26–28] and decreased the production of IFN-γ [29, 30]. In this study, HcESPs significantly inhibited the productions of IL-4 and IFN-γ, increased the level of IL-10.…”

Recombinant protein ofHaemonchus contortussmall GTPase ADP-ribosylation factor 1 (HcARF1) modulate the cell mediated immune responsein vitro

“…It has been recognized that immune suppressive cytokine IL-10 secreted by inducible Treg cells (iT Reg ) suppress the IFN-γ production [ 49 , 50 ]. The generation of immune suppressive cytokine IL-10 might be an important tactic by which parasites could suppress the IFN-γ-dependent, cell-mediated immunity [ 51 , 52 ]. In our previous research we found that rHcESPs suppressed the immune response by increasing the IL-10 and decreasing IFN-γ production [ 40 ].…”

AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech

“…For instance, the human RNASET2 protein, which acts as a tumor suppressor in different types of cancer, has been reported to trigger the innate immune response by recruiting host macrophages endowed with oncosuppressive properties toward the tumor mass in vivo [13, 14]. Moreover, other members of the T2 RNase family have recently been shown to carry out a modulatory role in the immune response as well [15, 16]. …”