Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice
Sepsis is a disease caused by multiple microbial infections resulting in multiple organ failure. Schistosoma japonicum secreted cystatin (Sj-Cys) is a strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. To determine whether the therapeutic effec...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2024/8626082 |
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| author | Feifei Huang Yayun Qian Huihui Li Liang Chu Chen Wan Qili Shen Qianqian Li Xiuxiu Li Xinyue Wu Bin Zhan Rui Zhou Xiaodi Yang |
| author_facet | Feifei Huang Yayun Qian Huihui Li Liang Chu Chen Wan Qili Shen Qianqian Li Xiuxiu Li Xinyue Wu Bin Zhan Rui Zhou Xiaodi Yang |
| author_sort | Feifei Huang |
| collection | DOAJ |
| description | Sepsis is a disease caused by multiple microbial infections resulting in multiple organ failure. Schistosoma japonicum secreted cystatin (Sj-Cys) is a strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. To determine whether the therapeutic effect of Sj-Cys on sepsis can be conveyed by the exosomes released by Sj-Cys-stimulated macrophages, RAW264.7 macrophages were stimulated with rSj-Cys in vitro, the exosomes were obtained from the cell culture supernatant by ultracentrifugation. Sepsis was induced in BALB/c mice by cecal ligation and puncture (CLP). The septic mice were treated with exosomes derived from Sj-Cys-treated macrophages. The treatment effect of exosomes on sepsis was assessed by examining the survival rate of mice up to 72 hr and measuring serum levels of inflammatory cytokines, liver/kidney damage biomarkers, and observing pathological changes in tissue sections. The tissue levels of M1, M2 macrophage surface markers, and TRL2/MyD88 were measured to explore possible mechanisms. Results. Exosomes derived from Sj-Cys-treated macrophages exhibited significant therapeutic effect on CLP-induced sepsis in mice with prolonged survival rate and less damage of critical organs by downregulating the proinflammatory factors TNF-α and IL-6 and upregulating the anti-inflammatory factor TGF-β. The therapeutic effect of exosomes is associated with macrophage polarization from M1 to M2 in the infected tissues via downregulating TRL2/MyD88 inflammatory pathway. Conclusions. Exosomes derived from Sj-Cys-treated macrophages attenuated sepsis in mice through promoting macrophage polarization from M1 to M2 and reducing inflammatory responses, possibly via downregulating TLR2/MyD88 inflammatory signaling pathway. This offers new approaches for immunotherapy of sepsis. |
| format | Article |
| id | doaj-art-7c0d9a00bc4f4b9d8a2b479122187aed |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-7c0d9a00bc4f4b9d8a2b479122187aed2025-02-03T06:14:52ZengWileyJournal of Immunology Research2314-71562024-01-01202410.1155/2024/8626082Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in MiceFeifei Huang0Yayun Qian1Huihui Li2Liang Chu3Chen Wan4Qili Shen5Qianqian Li6Xiuxiu Li7Xinyue Wu8Bin Zhan9Rui Zhou10Xiaodi Yang11First Affiliated Hospital of Bengbu Medical CollegeFirst Affiliated Hospital of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeNational School of Tropical MedicineFirst Affiliated Hospital of Bengbu Medical CollegeAnhui Key Laboratory of Infection and Immunity of Bengbu Medical CollegeSepsis is a disease caused by multiple microbial infections resulting in multiple organ failure. Schistosoma japonicum secreted cystatin (Sj-Cys) is a strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. To determine whether the therapeutic effect of Sj-Cys on sepsis can be conveyed by the exosomes released by Sj-Cys-stimulated macrophages, RAW264.7 macrophages were stimulated with rSj-Cys in vitro, the exosomes were obtained from the cell culture supernatant by ultracentrifugation. Sepsis was induced in BALB/c mice by cecal ligation and puncture (CLP). The septic mice were treated with exosomes derived from Sj-Cys-treated macrophages. The treatment effect of exosomes on sepsis was assessed by examining the survival rate of mice up to 72 hr and measuring serum levels of inflammatory cytokines, liver/kidney damage biomarkers, and observing pathological changes in tissue sections. The tissue levels of M1, M2 macrophage surface markers, and TRL2/MyD88 were measured to explore possible mechanisms. Results. Exosomes derived from Sj-Cys-treated macrophages exhibited significant therapeutic effect on CLP-induced sepsis in mice with prolonged survival rate and less damage of critical organs by downregulating the proinflammatory factors TNF-α and IL-6 and upregulating the anti-inflammatory factor TGF-β. The therapeutic effect of exosomes is associated with macrophage polarization from M1 to M2 in the infected tissues via downregulating TRL2/MyD88 inflammatory pathway. Conclusions. Exosomes derived from Sj-Cys-treated macrophages attenuated sepsis in mice through promoting macrophage polarization from M1 to M2 and reducing inflammatory responses, possibly via downregulating TLR2/MyD88 inflammatory signaling pathway. This offers new approaches for immunotherapy of sepsis.http://dx.doi.org/10.1155/2024/8626082 |
| spellingShingle | Feifei Huang Yayun Qian Huihui Li Liang Chu Chen Wan Qili Shen Qianqian Li Xiuxiu Li Xinyue Wu Bin Zhan Rui Zhou Xiaodi Yang Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice Journal of Immunology Research |
| title | Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice |
| title_full | Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice |
| title_fullStr | Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice |
| title_full_unstemmed | Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice |
| title_short | Exosomes Derived from Schistosoma japonicum Cystatin-Treated Macrophages Attenuated CLP-Induced Sepsis in Mice |
| title_sort | exosomes derived from schistosoma japonicum cystatin treated macrophages attenuated clp induced sepsis in mice |
| url | http://dx.doi.org/10.1155/2024/8626082 |
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