What question did this study set out to answer?

This research aims to understand how blocking ST2 affects immune responses and fibrosis in alveolar echinococcosis.

June 18, 2026Open Access

ST2 blockade modulates IL-33–driven immune responses and is associated with reduced hepatic fibrosis in alveolar echinococcosis

Key Points

This research aims to understand how blocking ST2 affects immune responses and fibrosis in alveolar echinococcosis.
Established a murine model of alveolar echinococcosis in C57BL/6 mice consisting of three groups: untreated infected, anti-ST2 treated infected, and uninfected controls.
Assessed liver pathology and fibrosis using various staining techniques and examined immune and fibrotic markers through immunohistochemistry and immunofluorescence.
Analyzed liver samples from humans with AE for translational relevance, measuring systemic cytokine profiles to evaluate immune modulation.
ST2 blockade significantly reduced metacestode lesion size and hepatic tissue invasion in infected mice.
There was lower expression of fibrosis markers, including α-smooth muscle actin and collagen I, post anti-ST2 treatment.
Treatment led to decreased hepatic infiltration of immune cells like CD4⁺ T cells and M2 macrophages, alongside lower systemic cytokine levels.

Abstract

Abstract Background Infection with Echinococcus multilocularis causes alveolar echinococcosis (AE), a severe parasitic disease characterised by progressive hepatic infiltration and fibrosis. Current treatment options remain limited, and the immune-mediated mechanisms underlying fibrosis are not fully understood. This study investigated the role of the IL-33/ST2 axis in AE-associated immunopathology and evaluated the effects of ST2 blockade in an experimental model. Methods A murine model of AE was established in C57BL/6 mice, which were allocated to untreated infected, anti-ST2–treated infected and uninfected control groups. Liver pathology and fibrosis were assessed using haematoxylin and eosin staining, Masson’s trichrome staining and transmission electron microscopy. Immune and fibrotic markers were analysed by immunohistochemistry and immunofluorescence. In parallel, liver samples from patients with AE were examined to evaluate translational relevance. Systemic cytokine profiles were quantified to assess immune modulation. Results Analysis of human AE liver samples showed an increased expression of IL-33/ST2 and associated immune and fibrotic markers, consistent with findings in the experimental mouse model. In infected mice, ST2 blockade significantly reduced metacestode lesion size and hepatic tissue invasion. This was accompanied by reduced fibrosis, as indicated by lower expression of α-smooth muscle actin, collagen I, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1. Anti-ST2 treatment was also associated with reduced hepatic infiltration of CD4⁺ T cells, B cells and M2 macrophages, along with decreased systemic levels of IFN-γ, TNF-α, IL-4, IL-13, IL-17 and IL-1β. Conclusions ST2 blockade reduced metacestode growth and was associated with attenuated hepatic inflammation and fibrosis, supporting a role for IL-33/ST2 signalling in AE progression. Given the concurrent reduction in parasite burden, further studies are needed to determine whether the anti-fibrotic effects of ST2 inhibition are independent of parasite control.

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