Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Yan, Chao; Li, Xiangyang; Li, Bo; Zhang, Beibei; Jiang-tao, XU; Hua, Hui; Yu, Qian; Liu, Zhuan-Zhuan; Fu, Lei; Tang, Renxian; Zheng, Kuiyang

doi:10.3855/jidc.6698

Cited by 32 publications

(37 citation statements)

References 34 publications

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“…However, prolonged inflammation through excessive production of inflammatory cytokines and chemokines via TLR-mediated signaling could be detrimental because it may cause host toxicity and tissue damage. In the mouse model of clonorchiasis, the expressions of TLR2 and TLR4 were upregulated during the infestation of C. sinensis , indicating probable participation of TLR2 and TLR4 in the stimulation of innate immune response during C. sinensis infestation (49). The T H 1-based inflammatory consequences instructed by TLRs are not only involved in eliminating pathogenic infections but can also induce fatal pathogenic consequences (50).…”

Section: Pathogenesis and Carcinogenesismentioning

confidence: 99%

Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review

et al. 2016

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Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier 8th National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA.

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Section: Pathogenesis and Carcinogenesismentioning

confidence: 99%

Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review

et al. 2016

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“…sinensis were successful to develop mature in this strain mouse and the levels of TLR4 were highly increased on days of 28 post-infection in C . sinensis -infected C3H mice, compared with health normal mice 11 . Based on these observations, to determine whether TLR4 involves in the PABF or not, we developed C .…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies showed that TLR4 was highly expressed in the activated HSC cells and myofibroblasts during C . sinensis -caused biliary fibrosis 11 , but the exact role of TLR4 in the pathological process of PABF caused by C . sinensis still remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis

Yan

Fan

et al. 2017

Sci Rep

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Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice. The results showed that the levels of collagen depositions, α-SMA and hydroxyproline (Hyp) contents in TLR4mut mice infected by C. sinensis were significantly lower than in those of TLR4wild ones. Furthermore, we found that the activation of TGF-β signaling was impaired in the TLR4mut mice, compared with wild mice when they were challenged to the same dose of C. sinensis metacercariae. Moreover, the mice with TLR4 mutation showed a decreased activation of hepatic stellate cells indicated by the expression of α-SMA, when compared with TLR4wild mice. These data demonstrate that TLR4 contributes to PABF caused by C. sinensis and TLR4 signaling may be a potential medical target for treatment of PABF.

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“…Since TLRs recognize pathogen-associated molecular patterns that are expressed on infectious agents, host cells may recognize liver fluke ESPs through differential activation of TLRs, leading to either the development of effective immunity or pathologic progression, such as activation of the innate mucosal inflammation cascade. In the mouse model for clonorchiasis, the expression of TLR2 and 4 mRNA and proteins in infected livers is up-regulated relatively early in infection (day 28 post-infection), indicating that both TLR2 and TLR4 participate in the stimulation of the innate immune response during C. sinensis infection [20]. …”

mentioning

confidence: 99%

Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells

Bahk

Pak

2016

Korean J Parasitol

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Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

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Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Cited by 32 publications

References 34 publications

Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review

Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review

The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis

Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells

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