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TLR3 activation by Clonorchis sinensis infection alleviates the fluke-induced liver fibrosis.
- Source :
-
PLoS Neglected Tropical Diseases . 5/11/2023, Vol. 17 Issue 5, p1-21. 21p. - Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19352727
- Volume :
- 17
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- PLoS Neglected Tropical Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 163667052
- Full Text :
- https://doi.org/10.1371/journal.pntd.0011325