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

Kan, Shuo; Li, Qi; Li, Hongmei; Yao, Yanhua; Du, Xin-Yue; Wu, Ching Ching; Chen, Guangjie; Guo, Xin; Qian, Men-Bao; Wang, Zhaojun

doi:10.1371/journal.pntd.0010726

Cited by 3 publications

(4 citation statements)

References 44 publications

(56 reference statements)

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“…A study emphasized the potential risk of latent infection reactivation in individuals undergoing immunosuppressive anti-TNF treatment[ 12 ]. Additionally, another study supported a notable link between C. sinensis infection and immune suppression, influenced by gender dynamics[ 15 ]. Notably, AS patients with parasitic infection may undergo treatment using non-steroidal anti-inflammatory agents.…”

Section: Discussionmentioning

confidence: 97%

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

Yi,

Liu,

Leng

et al. 2024

World J Clin Cases

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BACKGROUND Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease. The prevailing theory links AS onset to infections in susceptible individuals. Furthermore, infections may impair the immune responses. Numerous studies have investigated links between AS and various infections-bacterial, viral, fungal, and other microorganism infections. However, limited attention has been given to the association between AS and Clonorchis sinensis (C. sinensis ) infection. CASE SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation. Ten years ago, the patient had achieved a stable condition after treatment with biological agents. However, he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission. A lumbosacral magnetic resonance imaging (MRI) scan revealed bone marrow edema in the left sacroiliac joint, and laboratory indicators were elevated. Moreover, the presence of C. sinensis eggs was detected in the stool. The patient was prescribed praziquantel, resulting in the disappearance of C. sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain. A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint. CONCLUSION C. sinensis infections could potentially trigger the exacerbation of AS. Clinicians should pay attention to investigating the presence of infections.

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Section: Discussionmentioning

confidence: 97%

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

Yi,

Liu,

Leng

et al. 2024

World J Clin Cases

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“…It was believed that the disparity in C . sinensis infection rates between sexes primarily stemmed from dietary habits, particularly the consumption of raw fish [ 33 ]. This behavior has contributed to a higher prevalence of C .…”

Section: Discussionmentioning

confidence: 99%

“…In alignment with Yuan Kuan Li et al's research on the correlation between C. sinensis infection and HCC [9], our results revealed that C. sinensis was highly related to HCC malignant behavior as exemplified by the BCLC stage and MVI. It was believed that the disparity in C. sinensis infection rates between sexes primarily stemmed from dietary habits, particularly the consumption of raw fish [33]. This behavior has contributed to a higher prevalence of C. sinensis infection among males compared to females [9,29].…”

Section: Sinensis Promotes Hcc By Activating Hcc Stemnessmentioning

confidence: 99%

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis

Lin,

Tang,

Qin

et al. 2024

PLoS Negl Trop Dis

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Background Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness. Methods A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann–Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan–Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens. Results Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19–9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM. Conclusion HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Author summary Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

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“…C. sinensis adult worm antigen (CsAWA) was prepared as described previously ( Kan et al., 2022 ). In brief, C. sinensis adult worms suspended in PBS were lysed by sonication in an ice-chilled water bath.…”

Section: Methodsmentioning

confidence: 99%

Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes

Li,

Kan

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionClonorchis sinensis infection results in various complications in the liver and biliary systems and is a neglected tropical disease in Eastern Asia. In this study, we report that C. sinensis calcium-binding protein Cs16 activates host immune cells and induces immunopathology in liver.MethodsImmunohistochemistry was used to detect the localization of Cs16 in C. sinensis adult worms. ELISA was used to detect the serum levels of anti-Cs16 IgG antibody in infected humans and mice. Bile duct injection model was used to figure out the role of Cs16 in vivo. RT-qPCR and ELISA were used to detect the cytokine production from Cs16-treated BMMs in vitro. Seahorse assay was used to detect the metabolic pathway of Cs16-treated BMMs in vitro.ResultCs16 localizes in the tegument and gut of C. sinensis. Humans and mice with C. sinensis infection exhibited increased levels of anti-Cs16-specific antibody. Using the bile duct injection technique, we found that Cs16 induced obvious inflammation and hepatic necrosis in vivo. Cs16 treatment caused the upregulation of inflammatory cytokines in innate immune cells. Moreover, Cs16-treated monocytes relied more on the glycolytic metabolic pathway.DiscussionOur findings suggest that Cs16 is a potential pathogenic factor derived from C. sinensis adult worm. By reprogramming the metabolic pathway of innate immune cells, Cs16 triggers pro-inflammatory responses in the liver, and therefore, Cs16 is a potential target for the prevention and treatment of clonorchiasis.

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

Cited by 3 publications

References 44 publications

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis

Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes

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