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Updated: Jul 16, 2025
Isolation And Dendritic Cell-Uptake of Small Extracellular Vesicles from Echinococcus granulosus
Published on: March 28, 2025
Echinococcus granulosus cyst fluid inhibits inflammatory responses through inducing histone demethylase KDM5B in
Xiaopeng Wang1,2, Ruolin Lin1,2, Chunxue Fu1,2
1NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Background:
Echinococcus granulosus cyst fluid (EgCF) weakens macrophage inflammatory responses, thereby enabling the parasite to evade the immune system. However, the role of histone modification in this process remains to be explored.
Methods:
The levels of IL-6, TNF-α, IL-10, H3K4me3, and KDM5B were detected using quantitative real-time PCR, ELISA, and Western blotting. The enrichment of H3K4me3 and KDM5B at the promoter of inflammatory factors was detected by chromatin immunoprecipitation.
Results:
Based on EgCF-stimulated macrophage models, we found that EgCF significantly inhibited mRNA expression and protein secretion of IL-6 and TNF-α and upregulated mRNA expression of IL-10 under the influence of TLR4. EgCF lowered the level of H3K4me3 and promoted the transcription and protein stability of histone demethylase KDM5B. Chromatin immunoprecipitation analysis revealed that EgCF suppressed the enrichment of H3K4me3 modification at the promoters of TNF-α and IL-6 and downregulated their expression in macrophages. Additionally, the inhibition of KDM5B activity by CPI-455 weakened the anti-inflammatory effect of EgCF.
Conclusions:
Our findings demonstrate a novel mechanism through which EgCF promotes KDM5B expression and inhibits the enrichment of H3K4me3 at the promoters of inflammatory cytokines to suppress the inflammatory response.
Insights
Echinococcus granulosus cyst fluid suppresses macrophage inflammation by promoting KDM5B expression and reducing H3K4me3 modification at inflammatory gene promoters. This epigenetic mechanism helps the parasite evade the host immune response.
Area of Science:
- Immunology
- Epigenetics
- Parasitology
Background:
- Echinococcus granulosus cyst fluid (EgCF) impairs macrophage inflammatory responses, aiding parasite immune evasion.
- The role of histone modifications in EgCF-induced immune suppression is not well understood.
Purpose of the Study:
- To investigate the epigenetic mechanisms by which EgCF modulates macrophage inflammatory responses.
- To explore the involvement of histone modification, specifically H3K4me3 and KDM5B, in EgCF's immune-evasive strategy.
Main Methods:
- Quantitative real-time PCR, ELISA, and Western blotting were used to measure cytokine (IL-6, TNF-α, IL-10) and protein levels (H3K4me3, KDM5B).
- Chromatin immunoprecipitation (ChIP) was employed to assess the enrichment of H3K4me3 and KDM5B at the promoters of inflammatory genes.
- Macrophage models stimulated with EgCF were utilized.
Main Results:
- EgCF inhibited IL-6 and TNF-α expression/secretion while upregulating IL-10 in macrophages, influenced by TLR4.
- EgCF decreased H3K4me3 levels and increased histone demethylase KDM5B transcription and stability.
- ChIP analysis showed EgCF suppressed H3K4me3 enrichment at TNF-α and IL-6 promoters, reducing their expression.
- Inhibiting KDM5B activity with CPI-455 diminished EgCF's anti-inflammatory effect.
Conclusions:
- EgCF employs a novel mechanism involving KDM5B upregulation and H3K4me3 reduction at inflammatory cytokine promoters.
- This epigenetic modulation effectively suppresses macrophage inflammatory responses, facilitating parasite survival.
