TLR3 activation by Clonorchis sinensis infection alleviates the fluke-induced liver fibrosis.

• Main Authors: Yuru Wang (Author), Pengtao Gong (Author), Xuancheng Zhang (Author), Xiaocen Wang (Author), Xu Zhang (Author), Nan Zhang (Author), Yanhui Yu (Author), Yeting Ma (Author), Haoyang Zhang (Author), Xichen Zhang (Author), Xin Li (Author), Jianhua Li (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2023-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Clonorchis sinensis is a zoonotic parasite associated with liver fibrosis and cholangiocarcinoma development. The role of toll-like receptors (TLRs) in C. sinensis infection has not yet been fully elucidated. Here, the TLR3 signaling pathway, cytokine expression and liver fibrosis were examined in C. sinensis-infected wildtype (WT) and TLR3-/- mice. Polyinosinic-polycytidylic acid (Poly (I:C)) was used to treat C. sinensis infections. The results showed that TLR3 deficiency caused severe clonorchiasis with increased parasite burden, exacerbated proinflammatory cytokine expression and liver lesions, promoted the TGF-β1/Smad2/3 pathway and myofibroblast activation, exacerbated liver fibrosis (compared to WT mice). Poly (I:C) intervention increased the body weight, decreased mouse mortality and parasite burden, reduced liver inflammation, and alleviated C. sinensis-induced liver fibrosis. Furthermore, C. sinensis extracellular vesicles (CsEVs) promote the production of IL-6, TNF in WT biliary epithelial cells (BECs) via p38/ERK pathway, compared with control group, while TLR3 deletion induced much higher levels of IL-6 and TNF in TLR3-/- BECs than that in WT BECs. Taken together, TLR3 inhibit IL-6 and TNF production via p38/ERK signaling pathway, a phenomenon that resulted in the alleviation of C. sinensis-induced liver fibrosis. Poly (I:C) is a potential treatment for clonorchiasis.

Item Description

1935-2727
1935-2735
10.1371/journal.pntd.0011325