Molecular Mechanisms of Clonorchis sinensis-Host Interactions and Implications for Vaccine Development

Koda, Stephane; Zhu, Xingquan; Zheng, Kuiyang; Yan, Chao

doi:10.3389/fcell.2021.781768

Cited by 8 publications

(11 citation statements)

References 91 publications

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“…These results were consistent with previous studies by Wang et al. and Kong et al., which demonstrated that Th2-type immune responses are primarily triggered during the adult stage of C. sinensis , aiding in the control of excessive inflammation and promoting tissue repair ( Kong et al., 2020 ; Wang et al., 2021 ; Koda et al., 2022 ). These results indicated that the parasitism of adult C. sinensis leads to severe liver damage, anemia, and systemic diseases in the host, particularly at 5 weeks post-infection.…”

Section: Discussionsupporting

confidence: 93%

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Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Zhan,

Wu,

Deng

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionClonorchiasis remains a serious global public health problem, causing various hepatobiliary diseases. However, there is still a lack of overall understanding regarding the molecular events triggered by Clonorchis sinensis (C. sinensis) in the liver.MethodsBALB/c mouse models infected with C. sinensis for 5, 10, 15, and 20 weeks were constructed. Liver pathology staining and observation were conducted to evaluate histopathology. The levels of biochemical enzymes, blood routine indices, and cytokines in the blood were determined. Furthermore, alterations in the transcriptome, proteome, and metabolome of mouse livers infected for 5 weeks were analyzed using multi-omics techniques.ResultsThe results of this study indicated that adult C. sinensis can cause hepatosplenomegaly and liver damage, with the most severe symptoms observed at 5 weeks post-infection. However, as the infection persisted, the Th2 immune response increased and symptoms were relieved. Multi-omics analysis of liver infected for 5 weeks identified 191, 402 and 232 differentially expressed genes (DEGs), proteins (DEPs) and metabolites (DEMs), respectively. Both DEGs and DEPs were significantly enriched in liver fibrosis-related pathways such as ECM-receptor interaction and cell adhesion molecules. Key molecules associated with liver fibrosis and inflammation (Cd34, Epcam, S100a6, Fhl2, Itgax, and Retnlg) were up-regulated at both the gene and protein levels. The top three metabolic pathways, namely purine metabolism, arachidonic acid metabolism, and ABC transporters, were associated with liver cirrhosis, fibrosis, and cholestasis, respectively. Furthermore, metabolites that can promote liver inflammation and fibrosis, such as LysoPC(P-16:0/0:0), 20-COOH-leukotriene E4, and 14,15-DiHETrE, were significantly up-regulated.ConclusionOur study revealed that the most severe symptoms in mice infected with C. sinensis occurred at 5 weeks post-infection. Moreover, multi-omics analysis uncovered predominant molecular events related to fibrosis changes in the liver. This study not only enhances our understanding of clonorchiasis progression but also provides valuable insights into the molecular-level interaction mechanism between C. sinensis and its host liver.

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Section: Discussionsupporting

confidence: 93%

“…According to reports, it takes approximately one month for C. sinensis juveniles to develop into adults within the host’s hepatobiliary ducts ( Qian et al., 2016 ; Koda et al., 2022 ). We constructed mouse models infected with C. sinensis from 5 to 20 weeks.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Zhan,

Wu,

Deng

et al. 2023

Front. Cell. Infect. Microbiol.

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“…were abnormally increased in groups DSS+ Cs and DSS+DXM, and the effect of DXM was not as ideal as that reported by Zhou et al [ 16 ], which are possibly due to the complex mixed immune responses caused by C . sinensis infection [ 37 ], and the different batches and dosage regimens of the drug.…”

Section: Discussionmentioning

confidence: 99%

Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice

Xie

et al. 2022

PLoS Negl Trop Dis

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Background Currently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD. Clonorchis sinensis (C. sinensis) mainly elicit Th2/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease (CsCP) and adult crude antigen (CsCA) of C. sinensis, and C. sinensis (Cs) infection on DSS-induced colitis mice. Methods BALB/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with rCsCP, CsCA or dexamethasone (DXM) every day, or Cs infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured. Results Compared with Cs infection, rCsCP and CsCA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, rCsCP was superior to CsCA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that CsCA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, rCsCP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1/Th17 cells. Conclusions Both rCsCP and CsCA showed good therapeutic effects on the treatment of acute colitis, but rCsCP is a better choice. rCsCP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12/IL-23r axis.

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“…Th2 type immune responses are characteristic features of human infection with multicellular parasites [3,19]. In laboratory animals, clonorchiasis, like other helminth infections, is a potent inducer of Th2 responses [8,20,21]. Choi et al studied antibody and cytokine responses in mice infected with C. sinensis and found that susceptibility to C. sinensis infection was associated with Th2 cytokine production, especially IL-4 [22].…”

Section: Discussionmentioning

confidence: 99%

Clonorchis sinensis infection modulates key cytokines for essential immune response impacted by sex

Kan

et al. 2022

PLoS Negl Trop Dis

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Infection with helminths can modulate the host immune response, which ultimately shape morbidity and mortality of the associated diseases. We studied key cytokines for essential immune response in sera from 229 southeastern China individuals infected with Clonorchis sinensis and 60 individuals without C. sinensis infection, and measured serum specific IgG and IgE against worms in these people. Individuals infected with C. sinensis had significantly higher antigen-specific IgG and IgE levels, which were positively correlated with egg counts in feces. However, less enhancement of IgE antibody was observed in females when compared to males with similar infection levels. C. sinensis infection caused diminished Th1 cytokines (IL-1β, IL-2, IL-12p70, IFN-γ and TNF-α), Th2 cytokine (IL-4), as well as Th17 cytokine (IL-17A) in sera, which showed decreasing trend by infection intensity. Notably, these phenotypes were more significant in females than those in males. Although C. sinensis infection is associated with the development of hepatobiliary diseases, there was no significant correlation between the dampened cytokine profiles and the hepatobiliary morbidities. Our study indicates C. sinensis infection is strongly related to the immune suppression in human. Sex differences shape the immune milieus of clonorchiasis. This study provides a better understanding of how worms affect immune responses and cause a long-term immune alternation in humans with C. sinensis infection.

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Molecular Mechanisms of Clonorchis sinensis-Host Interactions and Implications for Vaccine Development

Cited by 8 publications

References 91 publications

Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice

Clonorchis sinensis infection modulates key cytokines for essential immune response impacted by sex

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