Regulation of anti-inflammatory cytokines IL-10 and TGF-β in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen

Dendritic cells (DCs), which are regarded as the most potent antigen-presenting cells, are involved in innate and adaptive immunity. Upon uptake of pathogens, DCs express cell surface markers and secrete cytokines. In this study, we analyzed production of cytokines and found that interleukin (IL)-10 and transforming growth factor (TGF)-β production significantly increased in bone marrow-derived DCs and a mouse DC line, DC2.4, after treatment with crude antigen (CA) from liver fluke, Clonorchis sinensis. However, expression patterns of several activation molecules did not change. In addition, following treatment of DC2.4 cells with antigen from the lung fluke, Paragonimus westermani, production of IL-10 and TGF-β significantly increased compared with groups treated with other parasite antigens, Spirometra erinacei plerocercoid CA and Echinococcus granulosus hydatid cystic fluid. We also found that treatment of DC2.4 cells with C. sinensis CA resulted in rapid and significant phosphorylation of extracellular signal-regulated kinase 1/2, a mitogen-activated protein kinase. Following treatment of DC2.4 cells with C. sinensis CA, treatment with an inhibitor specific to an extracellular signal-regulated kinase inhibited production of IL-10 and TGF-β. Our results suggest that CA from C. sinensis has a role in the anti-inflammatory function of DC cells by inducing IL-10 and TGF-β through activation of extracellular signal-regulated kinase 1/2. Parasitic flukes may evade the body's defenses by promoting an anti-inflammatory response in the dendritic cells of the immune system, a research team from South Korea has shown. Young Mee Bae and colleagues from Seoul National University Medical Research Center exposed mouse dendritic cells to immune-triggering proteins derived from various helminth worms. Proteins from two tapeworm species (Spirometra erinacei and Echinococcus granulosus) had little effect; yet, proteins from two fluke species (Clonorchis sinensis and Paragonimus westermani) significantly increased levels of two anti-inflammatory cytokines: interleukin-10 and transforming growth factor beta. This effect was especially pronounced with proteins derived from C. sinensis, the Chinese liver fluke. Bae and colleagues showed that activation of an enzyme called extracellular signal-regulated kinase 1/2 helped to promote the secretion of the anti-inflammatory molecules from the dendritic cells.