1. CCL17 and CCL19 are markers of disease progression in alveolar echinococcosis.
- Author
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Chen J, Ma Y, Liu Y, Zhao H, Qi X, Sun Y, Zhou X, Zhou J, Ma X, and Wang L
- Subjects
- Animals, Humans, Mice, Echinococcosis metabolism, Liver Cirrhosis parasitology, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Disease Models, Animal, Liver parasitology, Liver metabolism, Liver pathology, Echinococcosis, Hepatic metabolism, Echinococcosis, Hepatic parasitology, Female, Male, Hepatocytes metabolism, Hepatocytes parasitology, Disease Progression, Biomarkers metabolism, Chemokine CCL19 metabolism, Chemokine CCL17 metabolism, Chemokine CCL17 genetics
- Abstract
Objectives: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality., Methods: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses., Results: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80., Conclusion: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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