Immune Modulation in Clonorchis Sinensis Infection

Clonorchis sinensis infection elicits a complex interplay between innate and adaptive immune compartments within the hepatobiliary environment. In early stages, parasite-derived excretory/secretory products engage pattern-recognition receptors on biliary epithelial cells and dendritic cells, triggering pro-inflammatory signals and recruitment of macrophages that adopt an M1 phenotype. As infection progresses, immune profiles shift towards Th2-dominant responses and the expansion of regulatory T cells, which secrete IL-10 and TGF-β to dampen inflammation. This dynamic polarisation supports parasite survival but also contributes to fibrogenesis by activating hepatic stellate cells via TGF-β/Smad and NF-κB pathways. Recent advances in multi-omics characterisation have illuminated the molecular cascades underlying tissue remodelling, while investigations into Toll-like receptor signalling and extracellular vesicle-mediated crosstalk have identified potential targets for intervention. Understanding immune modulation in clonorchiasis is critical for devising novel therapeutics and vaccines to curb global morbidity associated with biliary fibrosis and cholangiocarcinoma.

Research from Nature Portfolio

A foundational study revealed that mutation of Toll-like receptor 4 in a murine model markedly attenuates pathogen-associated biliary fibrosis. Mutant mice exhibited significantly reduced collagen deposition, α-smooth muscle actin expression and hydroxyproline content following infection, owing to impaired activation of TGF-β signalling and diminished hepatic stellate cell engagement. These results position TLR4 as a central mediator of fibrogenic cascades in clonorchiasis and suggest that modulation of this receptor could form the basis of targeted anti-fibrotic therapies.

Immune Modulation in Clonorchis Sinensis Infection publication trend

The graph below shows the total number of articles in immune modulation in clonorchis sinensis infection across all publications each year (not limited to Nature Index journals).

Technical terms

Toll-like receptor 4 (TLR4): A membrane receptor recognising pathogen-associated molecular patterns, critical for initiating pro-fibrotic signalling in bile ducts.

Toll-like receptor 3 (TLR3): A pattern-recognition receptor activated by double-stranded RNA, capable of modulating inflammation and fibrosis in helminth infections.

Th2 immune response: A branch of adaptive immunity characterised by IL-4, IL-5 and IL-13 production, associated with antibody class switching and tissue repair.

Regulatory T cell (Treg): A CD4+ T lymphocyte subset that secretes IL-10 and TGF-β to suppress excessive immune activation and maintain homeostasis.

Excretory/secretory products (ESPs): A collection of molecules released by parasites that interact with host cells to modulate immune responses and promote parasite survival.

References

1. Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver. Frontiers in Cellular and Infection Microbiology (2023).
2. TLR3 activation by Clonorchis sinensis infection alleviates the fluke-induced liver fibrosis. PLOS Neglected Tropical Diseases (2023).
3. Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4. Parasites & Vectors (2015).
4. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo. PLOS Neglected Tropical Diseases (2017).
5. Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis. PLOS ONE (2017).
6. The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis. Scientific Reports (2017).