The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice
Liver fibrosis can result from various causes and could progress to cirrhosis and cancer; however, there are no effective treatments due to that its molecular mechanism is unclear. liver fibrosis model made by Schistosoma japonicum (S. japonicum) infection or Carbon tetrachloride (CCl4) intraperiton...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.570524/full |
| _version_ | 1818316737783791616 |
|---|---|
| author | Li-Jun Song Li-Jun Song Li-Jun Song Xu-Ren Yin Sha-Sha Mu Jia-Huang Li Jia-Huang Li Jia-Huang Li Hong Gao Ying Zhang Pan-Pan Dong Cong-Jin Mei Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua |
| author_facet | Li-Jun Song Li-Jun Song Li-Jun Song Xu-Ren Yin Sha-Sha Mu Jia-Huang Li Jia-Huang Li Jia-Huang Li Hong Gao Ying Zhang Pan-Pan Dong Cong-Jin Mei Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua |
| author_sort | Li-Jun Song |
| collection | DOAJ |
| description | Liver fibrosis can result from various causes and could progress to cirrhosis and cancer; however, there are no effective treatments due to that its molecular mechanism is unclear. liver fibrosis model made by Schistosoma japonicum (S. japonicum) infection or Carbon tetrachloride (CCl4) intraperitoneal injection is a conventional model used in liver fibrosis-related studies for mechanism or pharmaceutical research purposes. But the differences in the pathological progression, immune responses and the underlying mechanism between the two liver fibrosis model have not been carefully compared and characterized, which hinders us from correctly understanding and making better use of the two models. In the present study, the pathological changes to the liver, and the cytokines, inflammatory factors, macrophages, and lymphocytes subsets involved were analyzed in the liver fibrosis model of S. japonicum infection or CCl4 intraperitoneal injection. Additionally, the pathological progression, immune responses and the underlying injury mechanism in these two models were compared and characterized. The results showed that the changing trend of interleukin-13 (IL-13), transforming growth factor beta (TGF-β), inflammatory factors, and M1, M2 macrophages, were consistent with the development trend of fibrosis regardless of whether liver fibrosis was caused by S. japonicum or CCl4. For lymphocyte subsets, the proportions of CD3+ T cells and CD4+ T cells decreased gradually, while proportion of CD8+ T cells peaked at 6 weeks in mice infected with S. japonicum and at 12 weeks in mice injected with CCl4. With prolonged S. japonicum infection time, Th1 (CD4+IFN-γ+) immunity converted to Th2 (CD4+IL-4+)/Th17 (CD4+IL-17+) with weaker regulatory T cell (Treg) (CD4+CD25+FOXP3+) immunity. However, in liver fibrosis caused by CCl4, Th1 cells occupied the dominant position, while proportions of Th2, Th17, and Treg cells decreased gradually. In conclusion, liver fibrosis was a complex pathological process that was regulated by a series of cytokines and immune cells. The pathological progressions and immune responses to S. japonicum or CCl4 induced liver fibrosis were different, possibly because of their different injury mechanisms. The appropriate animal model should be selected according to the needs of different experiments and the pathogenic factors of liver fibrosis in the study. |
| first_indexed | 2024-12-13T09:26:11Z |
| format | Article |
| id | doaj.art-96d2c4da9b51445cb6c774a859797c1c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T09:26:11Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-96d2c4da9b51445cb6c774a859797c1c2022-12-21T23:52:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.570524570524The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in MiceLi-Jun Song0Li-Jun Song1Li-Jun Song2Xu-Ren Yin3Sha-Sha Mu4Jia-Huang Li5Jia-Huang Li6Jia-Huang Li7Hong Gao8Ying Zhang9Pan-Pan Dong10Cong-Jin Mei11Zi-Chun Hua12Zi-Chun Hua13Zi-Chun Hua14School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaPublic Health Research Center, Jiangnan University, Wuxi, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaSchool of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu TargetPharma Laboratories Inc., Changzhou High-Tech Research Institute of Nanjing University, Changzhou, ChinaDepartment of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, ChinaSchool of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu TargetPharma Laboratories Inc., Changzhou High-Tech Research Institute of Nanjing University, Changzhou, ChinaLiver fibrosis can result from various causes and could progress to cirrhosis and cancer; however, there are no effective treatments due to that its molecular mechanism is unclear. liver fibrosis model made by Schistosoma japonicum (S. japonicum) infection or Carbon tetrachloride (CCl4) intraperitoneal injection is a conventional model used in liver fibrosis-related studies for mechanism or pharmaceutical research purposes. But the differences in the pathological progression, immune responses and the underlying mechanism between the two liver fibrosis model have not been carefully compared and characterized, which hinders us from correctly understanding and making better use of the two models. In the present study, the pathological changes to the liver, and the cytokines, inflammatory factors, macrophages, and lymphocytes subsets involved were analyzed in the liver fibrosis model of S. japonicum infection or CCl4 intraperitoneal injection. Additionally, the pathological progression, immune responses and the underlying injury mechanism in these two models were compared and characterized. The results showed that the changing trend of interleukin-13 (IL-13), transforming growth factor beta (TGF-β), inflammatory factors, and M1, M2 macrophages, were consistent with the development trend of fibrosis regardless of whether liver fibrosis was caused by S. japonicum or CCl4. For lymphocyte subsets, the proportions of CD3+ T cells and CD4+ T cells decreased gradually, while proportion of CD8+ T cells peaked at 6 weeks in mice infected with S. japonicum and at 12 weeks in mice injected with CCl4. With prolonged S. japonicum infection time, Th1 (CD4+IFN-γ+) immunity converted to Th2 (CD4+IL-4+)/Th17 (CD4+IL-17+) with weaker regulatory T cell (Treg) (CD4+CD25+FOXP3+) immunity. However, in liver fibrosis caused by CCl4, Th1 cells occupied the dominant position, while proportions of Th2, Th17, and Treg cells decreased gradually. In conclusion, liver fibrosis was a complex pathological process that was regulated by a series of cytokines and immune cells. The pathological progressions and immune responses to S. japonicum or CCl4 induced liver fibrosis were different, possibly because of their different injury mechanisms. The appropriate animal model should be selected according to the needs of different experiments and the pathogenic factors of liver fibrosis in the study.https://www.frontiersin.org/article/10.3389/fimmu.2020.570524/fullliver fibrosisSchistosoma japonicumcarbon tetrachloridehepatic inflammationimmune responsedynamic progression |
| spellingShingle | Li-Jun Song Li-Jun Song Li-Jun Song Xu-Ren Yin Sha-Sha Mu Jia-Huang Li Jia-Huang Li Jia-Huang Li Hong Gao Ying Zhang Pan-Pan Dong Cong-Jin Mei Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice Frontiers in Immunology liver fibrosis Schistosoma japonicum carbon tetrachloride hepatic inflammation immune response dynamic progression |
| title | The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice |
| title_full | The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice |
| title_fullStr | The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice |
| title_full_unstemmed | The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice |
| title_short | The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice |
| title_sort | differential and dynamic progression of hepatic inflammation and immune responses during liver fibrosis induced by schistosoma japonicum or carbon tetrachloride in mice |
| topic | liver fibrosis Schistosoma japonicum carbon tetrachloride hepatic inflammation immune response dynamic progression |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.570524/full |
| work_keys_str_mv | AT lijunsong thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT lijunsong thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT lijunsong thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT xurenyin thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT shashamu thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT honggao thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT yingzhang thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT panpandong thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT congjinmei thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua thedifferentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT lijunsong differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT lijunsong differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT lijunsong differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT xurenyin differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT shashamu differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT jiahuangli differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT honggao differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT yingzhang differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT panpandong differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT congjinmei differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice AT zichunhua differentialanddynamicprogressionofhepaticinflammationandimmuneresponsesduringliverfibrosisinducedbyschistosomajaponicumorcarbontetrachlorideinmice |