In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 17, No. 5 ( 2023-5-11), p. e0011325-
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0011325
DOI:
10.1371/journal.pntd.0011325.g001
DOI:
10.1371/journal.pntd.0011325.g002
DOI:
10.1371/journal.pntd.0011325.g003
DOI:
10.1371/journal.pntd.0011325.g004
DOI:
10.1371/journal.pntd.0011325.g005
DOI:
10.1371/journal.pntd.0011325.g006
DOI:
10.1371/journal.pntd.0011325.g007
DOI:
10.1371/journal.pntd.0011325.g008
DOI:
10.1371/journal.pntd.0011325.g009
DOI:
10.1371/journal.pntd.0011325.g010
DOI:
10.1371/journal.pntd.0011325.s001
DOI:
10.1371/journal.pntd.0011325.s002
DOI:
10.1371/journal.pntd.0011325.s003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2429704-5
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