CD155 as a therapeutic target in alveolar echinococcosis: insights from an infection mouse model.

INTRODUCTION

Alveolar echinococcosis (AE) is a life-threatening zoonotic parasitic disease caused by the metacestode stage of , characterized by granulomatous lesions and liver fibrosis. Immune exhaustion is the key mechanism by which evades host immune responses and maintains long-term parasitism. Although CD155 is recognized as an immune checkpoint molecule, its specific role and underlying mechanism in AE remain unclear.

METHODS

A mouse model of infection was used to investigate the role of CD155 in AE progression. Flow cytometry, immunohistochemistry, and immunofluorescence were employed to assess CD155 expression and analyze T-cell function. In addition, liver weight, lesion size, lesion number, inflammation index, collagen deposition (via Masson staining), and stellate cell activation (via α-SMA immunohistochemistry) were statistically quantified in the CD155 hepatocyte knockout mice. Each experimental group included five mice ( = 5).

RESULTS

CD155 expression in hepatocytes was significantly increased-approximately 2-fold compared to Sham controls-and predominantly localized near lesion sites. The infected group showed significantly reduced percentages of functional CD4IFN-γ, CD4CD107a, and CD8CD107a T cells ( < 0.05), along with enrichment of exhausted TIGIT T cells adjacent to CD155 hepatocytes. , CD155 expression in hepatocytes was upregulated in a dose-dependent manner when co-cultured with metacestode vesicles, reaching 1.5-fold that of the control. Notably, hepatocyte-specific CD155 knockout in infected mice restored CD4 and CD8 T-cell function and reduced liver damage, as indicated by decreased lesion burden.

CONCLUSION

In the infection mouse model, excretory/secretory products from metacestode vesicles upregulated CD155 expression in hepatocytes, contributing to an immunosuppressive microenvironment and T-cell exhaustion. Targeting CD155 reverses this immunosuppression and mitigates hepatic pathology, highlighting CD155 as a promising therapeutic target for AE.