CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model
IntroductionAlveolar echinococcosis (AE) is a life-threatening zoonotic parasitic disease caused by the metacestode stage of Echinococcus multilocularis, characterized by granulomatous lesions and liver fibrosis. Immune exhaustion is the key mechanism by which E. multilocularis evades host immune re...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1624387/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849429188926242816 |
|---|---|
| author | Xue Zhang Liang Li Tao Sun Ning Yang Hui Liu Jin Chu Junlong Xue Guodong Lü Tuerganaili Aji Xiaojuan Bi Renyong Lin Renyong Lin |
| author_facet | Xue Zhang Liang Li Tao Sun Ning Yang Hui Liu Jin Chu Junlong Xue Guodong Lü Tuerganaili Aji Xiaojuan Bi Renyong Lin Renyong Lin |
| author_sort | Xue Zhang |
| collection | DOAJ |
| description | IntroductionAlveolar echinococcosis (AE) is a life-threatening zoonotic parasitic disease caused by the metacestode stage of Echinococcus multilocularis, characterized by granulomatous lesions and liver fibrosis. Immune exhaustion is the key mechanism by which E. multilocularis 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.MethodsA mouse model of E. multilocularis 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 (n = 5).ResultsCD155 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 CD4+IFN-γ+, CD4+CD107a+, and CD8+CD107a+ T cells (p < 0.05), along with enrichment of exhausted TIGIT+ T cells adjacent to CD155+ hepatocytes. In vitro, 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.ConclusionIn the E. multilocularis 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. |
| format | Article |
| id | doaj-art-778f7c6013e44fd296b54bfc95ee1fb0 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-778f7c6013e44fd296b54bfc95ee1fb02025-08-20T03:28:26ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.16243871624387CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse modelXue Zhang0Liang Li1Tao Sun2Ning Yang3Hui Liu4Jin Chu5Junlong Xue6Guodong Lü7Tuerganaili Aji8Xiaojuan Bi9Renyong Lin10Renyong Lin11State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaXinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaXinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Hepatobiliary and Hydatid Diseases, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaXinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaIntroductionAlveolar echinococcosis (AE) is a life-threatening zoonotic parasitic disease caused by the metacestode stage of Echinococcus multilocularis, characterized by granulomatous lesions and liver fibrosis. Immune exhaustion is the key mechanism by which E. multilocularis 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.MethodsA mouse model of E. multilocularis 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 (n = 5).ResultsCD155 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 CD4+IFN-γ+, CD4+CD107a+, and CD8+CD107a+ T cells (p < 0.05), along with enrichment of exhausted TIGIT+ T cells adjacent to CD155+ hepatocytes. In vitro, 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.ConclusionIn the E. multilocularis 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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1624387/fullEchinococcus multilocularisCD155T-cell exhaustionalveolar echinococcosismetacestode vesicles |
| spellingShingle | Xue Zhang Liang Li Tao Sun Ning Yang Hui Liu Jin Chu Junlong Xue Guodong Lü Tuerganaili Aji Xiaojuan Bi Renyong Lin Renyong Lin CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model Frontiers in Microbiology Echinococcus multilocularis CD155 T-cell exhaustion alveolar echinococcosis metacestode vesicles |
| title | CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model |
| title_full | CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model |
| title_fullStr | CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model |
| title_full_unstemmed | CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model |
| title_short | CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model |
| title_sort | cd155 as a therapeutic target in alveolar echinococcosis insights from an echinococcus multilocularis infection mouse model |
| topic | Echinococcus multilocularis CD155 T-cell exhaustion alveolar echinococcosis metacestode vesicles |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1624387/full |
| work_keys_str_mv | AT xuezhang cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT liangli cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT taosun cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT ningyang cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT huiliu cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT jinchu cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT junlongxue cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT guodonglu cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT tuerganailiaji cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT xiaojuanbi cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT renyonglin cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel AT renyonglin cd155asatherapeutictargetinalveolarechinococcosisinsightsfromanechinococcusmultilocularisinfectionmousemodel |