Limits...
Th17 down-regulation is involved in reduced progression of schistosomiasis fibrosis in ICOSL KO mice.

Wang B, Liang S, Wang Y, Zhu XQ, Gong W, Zhang HQ, Li Y, Xia CM - PLoS Negl Trop Dis (2015)

Bottom Line: The results showed that ICOSL KO mice exhibited improved survival, reduced liver granulomatous inflammation around parasite eggs, markedly inhibited hepatic fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2-related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF-β1, but higher level of Th1-related cytokine (IFN-γ) compared to wild-type (WT) mice.The reduced progression of fibrogenesis was correlated with the down-regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.Our findings suggest that IL-17-producing cells contribute to the hepatic granulomatous inflammation and subsequent fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Medical College of Soochow University, Suzhou,Jiangsu Province, The Peoples Republic of China.

ABSTRACT

Background: Granulomatous and fibrosing inflammation in response to parasite eggs is the main pathology that occurs during infection with Schistosoma spp. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis,and coordinate many types of immune cells that contribute to fibrosis. ICOSL plays an important role in controlling specific aspects of T cell activation, differentiation, and function. Previous work has suggested that ICOS is essential for Th17 cell development. However, the immunopathogenesis of this pathway in schistosomiasis fibrosisis still unclear.

Methodology/principal findings: Using models of schistosomiasis in ICOSL KO and the C57BL/6 WT mice, we studied the role of the ICOSL/ICOS interaction in the mediation of the Th17 response in host granulomatous inflammation, particularly in liver fibrosis during S. japonicum infection, and investigated the immune responses and pathology of ICOSL KO mice in these models. The results showed that ICOSL KO mice exhibited improved survival, reduced liver granulomatous inflammation around parasite eggs, markedly inhibited hepatic fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2-related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF-β1, but higher level of Th1-related cytokine (IFN-γ) compared to wild-type (WT) mice. The reduced progression of fibrogenesis was correlated with the down-regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.

Conclusions/significance: Our findings suggest that IL-17-producing cells contribute to the hepatic granulomatous inflammation and subsequent fibrosis. Importantly, there was a clearly positive correlation between the presence of IL-17-producing cells and ICOS expression in ICOSL KO mice, and additional results indicated that Th17 was involved in the pathological tissue remodeling in liver fibrosis induced by schistosomiasis.

Show MeSH

Related in: MedlinePlus

Reduced liver fibrogenesis of schistosomiasis in ICOSL KO mice.The degree of hepatic fibrosis was accessed by staining collagen using Masson Trichrome method. Each mouse was sacrificed at 4, 7, 12 and 16 weeks post-infection and liver tissue was examined for collagen expression. (A). Liver fibrosis as determined by Masson staining (original magnification×400). The blue area represents fibrillar collagen and arrow shows eggs of S. japonicum. (B). The fibrosis area of the section was quantified using image-Pro Plus 6.0 software, the ratio of collagen area and total area (%) was counted and compared between ICOSL KO and WT mice. Data shown are pooled from two independent experiments. Symbols denotes the mean of ten different field of individual liver sample and lines denote mean values. Open symbols represent ICOS KO mice and closed symbols represent WT mice. §Significant genotype effect and * significant time effect (P< 0.05, Tukey HSD, ANOVA performed using combined data from two separate experiments).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4295877&req=5

pntd.0003434.g006: Reduced liver fibrogenesis of schistosomiasis in ICOSL KO mice.The degree of hepatic fibrosis was accessed by staining collagen using Masson Trichrome method. Each mouse was sacrificed at 4, 7, 12 and 16 weeks post-infection and liver tissue was examined for collagen expression. (A). Liver fibrosis as determined by Masson staining (original magnification×400). The blue area represents fibrillar collagen and arrow shows eggs of S. japonicum. (B). The fibrosis area of the section was quantified using image-Pro Plus 6.0 software, the ratio of collagen area and total area (%) was counted and compared between ICOSL KO and WT mice. Data shown are pooled from two independent experiments. Symbols denotes the mean of ten different field of individual liver sample and lines denote mean values. Open symbols represent ICOS KO mice and closed symbols represent WT mice. §Significant genotype effect and * significant time effect (P< 0.05, Tukey HSD, ANOVA performed using combined data from two separate experiments).

Mentions: Masson trichrome stained sections of liver showed typical pathological characteristics of liver of schistosomiasis with remarkable acute granuloma formation and subsequent liver fibrosis from week 7 through week 16 (Fig. 6A). Moreover, analysis of Mason trichrome staining showed that the ICOSL KO group developed mild hepatic fibrosis and reduced collagen production compared to WT mice (Fig. 6B).


Th17 down-regulation is involved in reduced progression of schistosomiasis fibrosis in ICOSL KO mice.

Wang B, Liang S, Wang Y, Zhu XQ, Gong W, Zhang HQ, Li Y, Xia CM - PLoS Negl Trop Dis (2015)

Reduced liver fibrogenesis of schistosomiasis in ICOSL KO mice.The degree of hepatic fibrosis was accessed by staining collagen using Masson Trichrome method. Each mouse was sacrificed at 4, 7, 12 and 16 weeks post-infection and liver tissue was examined for collagen expression. (A). Liver fibrosis as determined by Masson staining (original magnification×400). The blue area represents fibrillar collagen and arrow shows eggs of S. japonicum. (B). The fibrosis area of the section was quantified using image-Pro Plus 6.0 software, the ratio of collagen area and total area (%) was counted and compared between ICOSL KO and WT mice. Data shown are pooled from two independent experiments. Symbols denotes the mean of ten different field of individual liver sample and lines denote mean values. Open symbols represent ICOS KO mice and closed symbols represent WT mice. §Significant genotype effect and * significant time effect (P< 0.05, Tukey HSD, ANOVA performed using combined data from two separate experiments).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295877&req=5

pntd.0003434.g006: Reduced liver fibrogenesis of schistosomiasis in ICOSL KO mice.The degree of hepatic fibrosis was accessed by staining collagen using Masson Trichrome method. Each mouse was sacrificed at 4, 7, 12 and 16 weeks post-infection and liver tissue was examined for collagen expression. (A). Liver fibrosis as determined by Masson staining (original magnification×400). The blue area represents fibrillar collagen and arrow shows eggs of S. japonicum. (B). The fibrosis area of the section was quantified using image-Pro Plus 6.0 software, the ratio of collagen area and total area (%) was counted and compared between ICOSL KO and WT mice. Data shown are pooled from two independent experiments. Symbols denotes the mean of ten different field of individual liver sample and lines denote mean values. Open symbols represent ICOS KO mice and closed symbols represent WT mice. §Significant genotype effect and * significant time effect (P< 0.05, Tukey HSD, ANOVA performed using combined data from two separate experiments).
Mentions: Masson trichrome stained sections of liver showed typical pathological characteristics of liver of schistosomiasis with remarkable acute granuloma formation and subsequent liver fibrosis from week 7 through week 16 (Fig. 6A). Moreover, analysis of Mason trichrome staining showed that the ICOSL KO group developed mild hepatic fibrosis and reduced collagen production compared to WT mice (Fig. 6B).

Bottom Line: The results showed that ICOSL KO mice exhibited improved survival, reduced liver granulomatous inflammation around parasite eggs, markedly inhibited hepatic fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2-related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF-β1, but higher level of Th1-related cytokine (IFN-γ) compared to wild-type (WT) mice.The reduced progression of fibrogenesis was correlated with the down-regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.Our findings suggest that IL-17-producing cells contribute to the hepatic granulomatous inflammation and subsequent fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Medical College of Soochow University, Suzhou,Jiangsu Province, The Peoples Republic of China.

ABSTRACT

Background: Granulomatous and fibrosing inflammation in response to parasite eggs is the main pathology that occurs during infection with Schistosoma spp. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis,and coordinate many types of immune cells that contribute to fibrosis. ICOSL plays an important role in controlling specific aspects of T cell activation, differentiation, and function. Previous work has suggested that ICOS is essential for Th17 cell development. However, the immunopathogenesis of this pathway in schistosomiasis fibrosisis still unclear.

Methodology/principal findings: Using models of schistosomiasis in ICOSL KO and the C57BL/6 WT mice, we studied the role of the ICOSL/ICOS interaction in the mediation of the Th17 response in host granulomatous inflammation, particularly in liver fibrosis during S. japonicum infection, and investigated the immune responses and pathology of ICOSL KO mice in these models. The results showed that ICOSL KO mice exhibited improved survival, reduced liver granulomatous inflammation around parasite eggs, markedly inhibited hepatic fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2-related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF-β1, but higher level of Th1-related cytokine (IFN-γ) compared to wild-type (WT) mice. The reduced progression of fibrogenesis was correlated with the down-regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.

Conclusions/significance: Our findings suggest that IL-17-producing cells contribute to the hepatic granulomatous inflammation and subsequent fibrosis. Importantly, there was a clearly positive correlation between the presence of IL-17-producing cells and ICOS expression in ICOSL KO mice, and additional results indicated that Th17 was involved in the pathological tissue remodeling in liver fibrosis induced by schistosomiasis.

Show MeSH
Related in: MedlinePlus