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. 2023 Jun 1;12(6):793.
doi: 10.3390/pathogens12060793.

Blocking BAFF Alleviates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice

Panpan Dong  1 , Congjin Mei  1 , Yingying Yang  1 , Yonghua Zhou  1 , Yongliang Xu  1 , Lijun Song  1 , Chuanxin Yu  1
Affiliations

Blocking BAFF Alleviates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice

Panpan Dong et al. Pathogens. .

Abstract

Schistosomiasis is an immunopathogenic disease characterized by egg granuloma and fibrosis. The hepatic fibrosis of schistosomiasis is caused by the coordinated action of local immune cells, liver-resident cells and related cytokines around the eggs of the liver. B-cell-activating factor (BAFF), expressed in many cells, is an essential factor for promoting the survival, differentiation, and maturation of cells. The overexpression of BAFF is closely related to many autoimmune diseases and fibrosis, but has not been reported to play a role in liver fibrosis caused by schistosomiasis. In the study, we found that, during Schistosoma japonicum (S. japonicum) infection in mice, the level of BAFF and its receptor BAFF-R progressively increased, then decreased with the extension of infection time, which was consistent with the progression of hepatic granuloma and fibrosis. Anti-BAFF treatment attenuated the histopathological damage in the liver of infected mice. The average areas of individual granulomas and liver fibrosis in anti-BAFF treatment mice were significantly lower than those in control mice, respectively. Anti-BAFF treatment increased the IL-10, decreased IL-4, IL-6, IL-17A, TGF-β, and downregulated the antibody level against S. japonicum antigens. These results suggested that BAFF acts a strong player in the immunopathology of schistosomiasis. Anti-BAFF treatment may influence Th2 and Th17 responses, and reduce the inflammatory reaction and fibrosis of schistosomiasis liver egg granuloma. It is suggested that BAFF might be a prospective target for the development of new methods to treat schistosomiasis liver fibrosis.

Keywords: B-cell-activating factor; Schistosoma japonicum; anti-BAFF treatment; apoptosis; liver fibrosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The BAFF and BAFF-R levels were correlated with the progress of schistosomiasis japonicum. C57BL/6 mice were infected with 15 ± 2 S. japonicum cercariae via the abdominal skin. At 0, 3, 6 and 9 weeks following infection, sera, liver and spleen were collected for experimentation. (A) BAFF levels in serum. The levels of serum specific IgG antibody against the AWA (B) and SEA (C) were measured by ELISA. Cells in spleen were harvested and processed for FACS staining. Cells were stained for BAFF (D) and BAFF−R (F). BAFF+ cells (E) and BAFF−R+ cells (G) were summarized in line graphs. Hematoxylin and Eosin (H&E) staining (×100) (H) and Masson’s trichrome (J) staining (×100) are shown in liver slices. Masson trichrome staining was used to measure the size of granulomas (I) and collagen areas (K) around a single egg. The level of hydroxyproline in the liver (L) was determined. (M) Spleen index was expressed as spleen weight (mg)/body weight (g). (N) Adult worms’ burdens. (O) Eggs’ burdens. The mean and SEM values were calculated. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. 0 W group.
Figure 2
Figure 2
Anti-BAFF treatment suppressed the formation of liver granulomas and fibrosis in mice. C57BL/6 mice were infected with 15 ± 2 S. japonicum cercariae via the abdominal skin. At 7 weeks following infection, sera, liver and spleen were collected for experimentation. (A) Schematic diagram of the experimental design of anti-BAFF treatment for mice infected with S. japonicum. (B) The pathological changes were shown with representative hematoxylin and eosin (H&E) and Masson trichrome staining (×100). (C) Granuloma size and (D) collagen areas around a single egg were measured. (E) The level of hepatic hydroxyproline was determined. (F) The spleen index was expressed as weight of spleen (mg)/body weight (g). (G) Hepatic index was expressed as liver weight/body weight. (H) The average burden of adult worms per mouse of different group collected from portal and mesenteric vein. (I) The average egg burden per gram in liver tissue of different groups. (J) Serum BAFF level of mice in different groups. The mean values and the SEM values were calculated. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Figure 3
Figure 3
Effects of anti-BAFF treatment on the level of anti-SEA IgG, anti-AWA IgG and cytokines in serum. (A) Anti-SEA IgG levels, (B) Anti-AWA IgG levels, (C) IFN-γ levels, (D) TNF-α levels, (E) IL-4 levels, (F) IL-6 levels, (G) TGF-β levels, (H) IL-10 levels, (I) IL-17A levels were assayed. All experiments were performed in triplicate and the mean and SEM values were calculated. ns = not significant, * p < 0.05, ** p < 0.01,.
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