Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2.

Background Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C.sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll-like receptors (TLRs) and further triggers immune responses, which determines the outcome of the infection. However, the mechanisms by which pathogen-associated molecules patterns from C.sinensis interact with TLRs were poorly understood. In the present study, we assumed that the molecules from C. sinensis may regulate host immune responses via TLR2 signaling pathway. Methodology/Principal findings In the present study, we have identified a similar to 34 kDa CsHscB from C. sinensis which physically bound with TLR2 as demonstrated by molecular docking and pull-down assay. We also found that recombinant CsHscB (rCsHscB) potently activates macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-alpha, and IL-10, but rCsHscB failed to induce IL-10 in macrophages from Tlr2(-/-) mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high production of IL-10 in the wild-type (WT) but not in Tlr2(-/-) mice. Consistently, the phosphorylation of ERK1/2 was also attenuated in Tlr2(-/-) mice compared to the WT mice, after the treatment with rCsHscB. Conclusions/Significance Our data thus demonstrate that rCsHscB from C.sinensis interacts with TLR2 to be endowed with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology. Author summary Clonorchis sinensisis a kind of liver fluke whose infection can cause inflammation and, fibrosis around the bile ducts. As type I biological agents (carcinogens) Type, it can also cause bile ductal cancer. However, the mechanisms by which the parasite interacts with host cells and further induce serious sequences are poorly understood. Here, we found a similar to 34 kDa rCsHscB from C.sinensis that can bind with TLR2, a well-known pattern recognition receptor. Importantly, we found that rCsHscB could lead to the activation of macrophage and induce a strong production of cytokines such as IL-10 and IL-6 through the TLR2-mediated signaling pathway. Besides, the animal study demonstrated that rCsHscB induce a high production of IL-10 in the wild-type (WT) but not in Tlr2(-/-) mice. These data showed that rCsHscB from C. sinensis interacted with TLR2 have immune-regulatory abilities, which can be used for other inflammatory disorders in the future beyond parasitology.