CsHscB as a novel TLR2 agonist from carcinogenic liver fluke Clonorchis sinensis modulates host immune response

Clonorchis sinensis-a fluke dwelling on the intrahepatic bile ducts causes clonorchiasis. During C. sinensis infection, worm-host interaction results in activation of PRRs and further triggers immune responses which determine the outcome of infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interacted with TLRs were poorly understood. In the present study, we identified a ~34 kDa lipoprotein CsHscB from C. sinensis which physically bound with TLR2. We also found that recombinant CsHscB (rCsHscB) potently activated macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-α, and IL-10 in a TLR2-dependent manner 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 induction of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Our data thus demonstrate that rCsHscB from C. sinensis is an unidentified TLR2 agonist with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology.