PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model
Abstract Background Ischemia-induced inflammation is the primary pathological mechanism underlying cardiac tissue injury caused by myocardial infarction (MI). Trichinella spiralis cystatin (Ts-Cys) has been shown to regulate macrophage polarization and alleviate various inflammatory and immune-relat...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-025-06854-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849470021854560256 |
|---|---|
| author | Weixiao Zhang Wenhui Yin Hongtao Wang Lingqin Wu Chang Li Xinyu Peng Xiang Li Kaibo Jiang Huiqi Yang Chenyue Dang Erhe Gao Qiwang Jin Xiaodi Yang |
| author_facet | Weixiao Zhang Wenhui Yin Hongtao Wang Lingqin Wu Chang Li Xinyu Peng Xiang Li Kaibo Jiang Huiqi Yang Chenyue Dang Erhe Gao Qiwang Jin Xiaodi Yang |
| author_sort | Weixiao Zhang |
| collection | DOAJ |
| description | Abstract Background Ischemia-induced inflammation is the primary pathological mechanism underlying cardiac tissue injury caused by myocardial infarction (MI). Trichinella spiralis cystatin (Ts-Cys) has been shown to regulate macrophage polarization and alleviate various inflammatory and immune-related diseases. Programmed cell death-1 (PD-1) is a crucial checkpoint receptor molecule and highly involved in maintaining immune tolerance. In this study, our aims were to investigate whether recombinant Ts-Cys protein (rTs-Cys) could be used to treat MI with recruited macrophage-dominant myocardial inflammation and whether PD-1 is involved in the immunomodulation of Ts-Cys in inflammatory diseases. Methods MI models were established in wild-type (WT) and PD-1 knockout (PD-1−/−) mice, followed by the intraperitoneal injection of rTs-Cys. The survival rates of mice were observed for 28 days post-surgery and treatment. Cardiac function was assessed by echocardiography. Histopathological evaluation of heart tissue affected by infarction was conducted to examine local inflammatory cell infiltration and cardiac tissue damage. Real-time quantitative PCR was used to detect messenger RNA expression levels of vascular endothelial growth factor (VEGF) and the macrophage surface markers inducible nitric oxide synthase and arginase-1 in the MI area. Serological levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), were measured using an enzyme-linked immunosorbent assay. Bone marrow-derived macrophages from WT and PD-1−/− mice were used to assess the effects of rTs-Cys on macrophage polarization in vitro. Results In WT mice, rTs-Cys treatment significantly improved the 28-day survival rate and cardiac function, reduced local inflammatory cell infiltration and cardiac pathological damage and increased VEGF expression levels of MI mice. The therapeutic effect of rTs-Cys was associated with macrophage polarization from the pro-inflammatory M1 phenotype to the regulatory M2 phenotype with reduced levels of inflammatory cytokines (TNF-α and IL-6) and increased levels of regulatory cytokines (IL-10 and TGF-β), as determined by both in vivo and in vitro tests. However, this therapeutic effect of rTs-Cys on MI was significantly reduced in PD-1−/− mice, as reflected by the higher level of M1 macrophages, elevated levels of inflammatory cytokines and decreased levels of regulatory cytokines. Conclusions rTs-Cys promotes M2-type polarization of macrophages through the PD-1 pathway to alleviate MI in mice and is, therefore, a potential drug for the treatment of MI and other inflammation-related diseases with involvement of the PD-1 checkpoint molecule. Graphical Abstract |
| format | Article |
| id | doaj-art-7b9b6fe2133f429d9533771afef4c5ad |
| institution | Kabale University |
| issn | 1756-3305 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj-art-7b9b6fe2133f429d9533771afef4c5ad2025-08-20T03:25:16ZengBMCParasites & Vectors1756-33052025-06-0118111810.1186/s13071-025-06854-4PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice modelWeixiao Zhang0Wenhui Yin1Hongtao Wang2Lingqin Wu3Chang Li4Xinyu Peng5Xiang Li6Kaibo Jiang7Huiqi Yang8Chenyue Dang9Erhe Gao10Qiwang Jin11Xiaodi Yang12First Affiliated Hospital of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversitySchool of Laboratory Medicine, Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityFirst Affiliated Hospital of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityLewis Katz School of Medicine, Temple UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAnhui Key Laboratory of Infection and Immunity of Bengbu Medical UniversityAbstract Background Ischemia-induced inflammation is the primary pathological mechanism underlying cardiac tissue injury caused by myocardial infarction (MI). Trichinella spiralis cystatin (Ts-Cys) has been shown to regulate macrophage polarization and alleviate various inflammatory and immune-related diseases. Programmed cell death-1 (PD-1) is a crucial checkpoint receptor molecule and highly involved in maintaining immune tolerance. In this study, our aims were to investigate whether recombinant Ts-Cys protein (rTs-Cys) could be used to treat MI with recruited macrophage-dominant myocardial inflammation and whether PD-1 is involved in the immunomodulation of Ts-Cys in inflammatory diseases. Methods MI models were established in wild-type (WT) and PD-1 knockout (PD-1−/−) mice, followed by the intraperitoneal injection of rTs-Cys. The survival rates of mice were observed for 28 days post-surgery and treatment. Cardiac function was assessed by echocardiography. Histopathological evaluation of heart tissue affected by infarction was conducted to examine local inflammatory cell infiltration and cardiac tissue damage. Real-time quantitative PCR was used to detect messenger RNA expression levels of vascular endothelial growth factor (VEGF) and the macrophage surface markers inducible nitric oxide synthase and arginase-1 in the MI area. Serological levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), were measured using an enzyme-linked immunosorbent assay. Bone marrow-derived macrophages from WT and PD-1−/− mice were used to assess the effects of rTs-Cys on macrophage polarization in vitro. Results In WT mice, rTs-Cys treatment significantly improved the 28-day survival rate and cardiac function, reduced local inflammatory cell infiltration and cardiac pathological damage and increased VEGF expression levels of MI mice. The therapeutic effect of rTs-Cys was associated with macrophage polarization from the pro-inflammatory M1 phenotype to the regulatory M2 phenotype with reduced levels of inflammatory cytokines (TNF-α and IL-6) and increased levels of regulatory cytokines (IL-10 and TGF-β), as determined by both in vivo and in vitro tests. However, this therapeutic effect of rTs-Cys on MI was significantly reduced in PD-1−/− mice, as reflected by the higher level of M1 macrophages, elevated levels of inflammatory cytokines and decreased levels of regulatory cytokines. Conclusions rTs-Cys promotes M2-type polarization of macrophages through the PD-1 pathway to alleviate MI in mice and is, therefore, a potential drug for the treatment of MI and other inflammation-related diseases with involvement of the PD-1 checkpoint molecule. Graphical Abstracthttps://doi.org/10.1186/s13071-025-06854-4Myocardial infarctionMacrophageTrichinella spiralisPD-1InflammationImmunomodulation |
| spellingShingle | Weixiao Zhang Wenhui Yin Hongtao Wang Lingqin Wu Chang Li Xinyu Peng Xiang Li Kaibo Jiang Huiqi Yang Chenyue Dang Erhe Gao Qiwang Jin Xiaodi Yang PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model Parasites & Vectors Myocardial infarction Macrophage Trichinella spiralis PD-1 Inflammation Immunomodulation |
| title | PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model |
| title_full | PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model |
| title_fullStr | PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model |
| title_full_unstemmed | PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model |
| title_short | PD-1-dependent therapeutic effect of Trichinella spiralis cystatin on myocardial infarction in a mice model |
| title_sort | pd 1 dependent therapeutic effect of trichinella spiralis cystatin on myocardial infarction in a mice model |
| topic | Myocardial infarction Macrophage Trichinella spiralis PD-1 Inflammation Immunomodulation |
| url | https://doi.org/10.1186/s13071-025-06854-4 |
| work_keys_str_mv | AT weixiaozhang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT wenhuiyin pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT hongtaowang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT lingqinwu pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT changli pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT xinyupeng pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT xiangli pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT kaibojiang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT huiqiyang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT chenyuedang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT erhegao pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT qiwangjin pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel AT xiaodiyang pd1dependenttherapeuticeffectoftrichinellaspiraliscystatinonmyocardialinfarctioninamicemodel |