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Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model.

ABSTRACT: BACKGROUND:Potent granulomatous inflammation responses induced by schistosome eggs and resultant fibrosis are the primary causes of morbidity in schistosomiasis. Recombinant Sj16 (rSj16), a 16-kDa protein of Schistosoma japonicum produced in Escherichia coli, has been demonstrated to have novel immunoregulatory effects in vivo and in vitro. Thus, this study investigated the anti-inflammatory and anti-fibrotic effects of rSj16 treatment in S. japonicum-infected mice and demonstrated the immune modulation between the schistosome and the host. METHODS:Schistosoma japonicum infected mice were treated with the rSj16 protein and Sj16 peptide at different time points post-infection to assess their efficacy at the optimal time point. Sj16 peptide and/or Praziquantel (PZQ) treatments were initiated at week 5 post-infection to compare the therapeutic efficacy of each regimen. Hepatic granulomatous inflammation, fibrosis and cytokine production (pro-inflammatory, Th1, Th2, Th17 and regulatory cytokines IL-10) were detected. Moreover, M2 macrophages were measured to illuminate the mechanisms of Sj16. RESULTS:The rSj16 protein and Sj16 peptide had significant protective effects in S. japonicum-infected mice, as shown by decreased granuloma formation, areas of collagen deposition and inhibition of pro-inflammatory Th1, Th2 and Th17 cytokine production. These protective activities were more obvious when animals were treated with either the Sj16 protein or peptide at early stages post-infection. Interestingly, the combined treatment of PZQ and Sj16 was more effective and upregulated IL-10 production than administration of PZQ alone in infected mice. Furthermore, the Sj16 treatment alleviated the pathological effects associated with activated M2 macrophages. CONCLUSIONS:This study demonstrates the anti-inflammatory and anti-fibrotic effects of rSj16 in schistosomiasis. Therefore, the combination of rSj16 with PZQ could be a viable and promising therapeutic strategy for schistosomiasis. In addition, this investigation provides additional information on schistosome-mediated immune modulation and host-parasite interactions.

SUBMITTER: Shen J

PROVIDER: S-EPMC6755699 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model.

Shen Jia J Wang Lifu L Peng Mei M Liu Zhen Z Zhang Beibei B Zhou Tao T Sun Xi X Wu Zhongdao Z

Parasites & vectors 20190923 1

<h4>Background</h4>Potent granulomatous inflammation responses induced by schistosome eggs and resultant fibrosis are the primary causes of morbidity in schistosomiasis. Recombinant Sj16 (rSj16), a 16-kDa protein of Schistosoma japonicum produced in Escherichia coli, has been demonstrated to have novel immunoregulatory effects in vivo and in vitro. Thus, this study investigated the anti-inflammatory and anti-fibrotic effects of rSj16 treatment in S. japonicum-infected mice and demonstrated the i ...[more]

PMID: 31547847

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Project 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.

Dataset Information

Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model.

Publications

Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model.

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