Project description:In schistosomiasis japonica, the egg-induced granulomatous response and the development of extensive hepatic fibrosis is the main pathology. Information regarding the specific mechanisms associated with granuloma regression and the subsequent recovery events in the host liver are still limited. In this study, a murine model of schistosomiasis japonica was used to characterise the multicellular pathways occurring during liver regeneration. Schistosoma japonicum-infected C57BL/6 mice were administered with the drug praziquantel (PZQ), on a daily basis for five consecutive days to eliminate all adult parasites. The pathological changes of PZQ-treated groups after 3, 6 and 7 weeks post PZQ treatment were examined, along with the assessment of cellular infiltration to the liver. PZQ treatment significantly reduced the degree of splenomegaly, granuloma density and the collagen deposition of liver fibrosis. The infiltration of inflammatory cells, including neutrophils, eosinophils and macrophages to the liver were as well significantly decreased. Transcriptomic analysis revealed the significant up-regulation of fatty acid metabolism genes and the identification of peroxisome proliferator-activated receptor alpha (PPAR-α) as the upstream regulator during the process of liver recovery. Aryl hydrocarbon receptor (AhR) signalling pathway that is involved primarily in the regulation of hepatic enzymes responsible for xenobiotic metabolism was as well differentially up-regulated. These findings indicate that schistosome egg-induced fibrogenesis process is reversible, and provide a better understanding of the regression mechanisms associated with hepatic schistosomiasis. These results hold important implications for the future alleviation of this and other fibrotic diseases of clinical significance. C57BL/6 murine model infected with S. japonicum were treated orally with Praziquantel (PZQ) after 7 weeks post infection to examine the hepatic regression process following drug treatment. These PZQ-treated, non PZQ-treated and uninfected mice were then euthanised at 10, 13, and 14 weeks p.i. Livers were collected from each mice, and subjected to total RNA isolation and gene expression analysis. Microarray analysis of this study was performed using samples derived from 3 individual mice per group/time-point.

Project description:The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis. The gene expression profile of murine livers (BALB/c and CBA strains) were examined at 4, 7 and 9 weeks post infection with Schistosoma japonicum in comparison to that of uninfected controls. Three mice were utilised per group (Uninfected, 4, 7 and 9 weeks), totalling 24 samples. Microarray analysis was performed on individual RNA samples from each mouse.

Project description:The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Project description:Background: Schistosoma japonicum is a pathogen of the phylum Platyhelminths that causes zoonotic schistosomiasis endemic in China and Southeast Asian countries. Control of the disease has been hampered by the lack of efficient measures. The development of tools for diagnosis of acute and chronic infection, and novel antiparasite reagents all relies on the understanding of the biological mechanism of the parasite. Results: In this study, the polyadenylated transcripts from the male and female S. japonicum were sequenced by a high-through-put RNA-seq technique. Bioinformatic and experimental analyses were focused on the posttranscriptional RNA processing, which at the first time revealed the extensive alternative splicing events occurred in the adult stage of the parasite. The number of protein-coding sequences identified in the transcriptomes of the female and male S. japonicum was 15,939 and 19,501 respectively, which is more than that predicted from the annotated genome sequence. Further, we identified four types of posttranscriptional processing, also called alternative splicing, in both female and male worms of S. japonicum, including exon skipping, intron retention, alternative donor site, and alternative acceptor site. Unlike mammalian organisms, alternative donor site and alternative acceptor site were found to be more common than the other two types of posttranscriptional processing in S. japonicum. In total, 13,438 and 16,507 alternative splicing events were respectively predicted in the transcriptomes of female and male S. japonicum. Conclusions: By using RNA-seq technology, we obtained the global transcriptomes of male and female S. japonicum. These results further provide a comprehensive view of the global transcriptome of S. japonicum. The findings of a substantial level of alternative splicing events dynamically occurring in the parasitation of the S. japonicum in the mammalian hosts suggested a complicate transcriptional and post-transcriptional regulation mechanisms employed by the parasite. The data will not only significantly improve the re-annotation of the genome sequences, but will also provide new information in the biology of the parasite. Two samples are analyzed.

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Gene expression in the Schistosoma japonicum infected spleen

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