Project description:More than 40 species of mammal have been reported to be infected naturally with Schistosoma japonicum (Chinese mainland strain) in China. The reed vole, Microtus fortis, is the only known mammalian host in which the schistosomes are unable to mature and cause significant pathogenic changes. Gene expression profiling of the 10 day old schistosomula was performed. Microarray analysis was also used to identify differences in gene expression between Schistosoma japonicum schistosomula from BALB/c mice and from Microtus fortis. 10 day old schistosomula were isolated, total RNA obtained and Agilent one colour labeling used. A custom designed Agilent microarray was used to determine what differential gene expression occurs between parasites maintained in either a permissive (mouse) or non-permissive (vole) hosts.
Project description:More than 40 species of mammal have been reported to be infected naturally with Schistosoma japonicum (Chinese mainland strain) in China. The reed vole, Microtus fortis, is the only known mammalian host in which the schistosomes are unable to mature and cause significant pathogenic changes. Gene expression profiling of the 10 day old schistosomula was performed.
Project description:More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum); Microtus fortis (M. fortis), a species of vole, is the only mammal in which the schistosomes cannot mature or cause significant pathogenic changes. In the current study, we compared the differences in pathology by Hematoxylin-eosin staining and in changes in the T cell subsets with flow cytometry as well as gene expression using genome oligonucleotide microarrays in the lung and liver, before challenge and 10 days post-infection with schistosomes in a S. japonicum-susceptible mouse model of infection, a non-susceptible rat model and the non-permissive host, M. fortis. The results demonstrated that S. japonicum promoted a more intensive immune response and more pathological lesions in M. fortis and rats than in mice. Hematoxylin-eosin staining revealed that the immune effector cells involved were mainly eosinophilic granulocytes supplemented with heterophilic granulocytes and macrophages. The analysis of splenic T cell subsets showed that CD4+ T cell subsets and the CD4+/CD8+ ratio were increased while the CD8+ T cell subsets decreased remarkably in rats; whereas the CD8+ T cell subsets were increased but the CD4+/CD8+ ratio was decreased significantly in mice. The analysis of the pattern of gene expression suggested that some immune-associated genes and apoptosis-inducing genes upregulated while some development-associated genes were downregulated in the infected M. fortis compared to the uninfected controls; the three different hosts have different response mechanisms to schistosome infection. The results of this study will be helpful for identifying the key molecules in the immune response to S. japonicum in M. fortis and for understanding more about the underlying mechanism of the response, as well as for elucidating the interaction between S. japonicum and its hosts. This SuperSeries is composed of the SubSeries listed below.
Project description:Migrating schistosomula are an important stage of the schistosome lifecycle and represent a key target for elimination of infection by natural and vaccine induced host immune responses. To gain a better understanding of how these parasites initiate a primary host immune response we have characterised the host lung response to migrating Schistosoma japonicum schistosomula using a combination of histochemistry, microarrays and quantitative cytokine analysis. Our data suggest that, during a S. japonicum infection, actively migrating schistosomula induce a Type-2 cytokine response in the lung that may support the subsequent development of a CD4+ T helper 2 (Th2) response against egg antigens. This hypothesis is supported by the fact that schistosomula and schistosome eggs are known to express important Th2-inducing antigens such as omega-1, peroxiredoxin, kappa-5 and IPSE/alpha1. The host lung response to migrating schistosomula was associated with increased numbers of macrophages and expression of markers for alternatively activated macrophages (AAMφ) in the lung. Activation of AAMφ in the lung and at the systemic level could lead to the modulation of the host immune response to favour parasite survival. Induction of these cells could also contribute to diminished inflammatory responses to, for example, allergy and asthma that are known to be associated with helminth infections. These data enhance our understanding of the mechanisms whereby schistosomes may evade the immune response and the mechanisms by which schistosome infection can help influence the host response following exposure to allergenic stimuli. The gene expression profile of the murine lung was examined at 3 days weeks post infection with 500 Schistosoma japonicum cercariae in comparison to that of uninfected controls. Microarray analysis was performed on cRNA synthesised from total RNA derived from the lungs of 3 individual mice per group.
Project description:Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type. BioProject accession number is PRJNA290970, and the SRA Study accession number is SRP061588. Mixed sample of cDNA libaraies of Schistosomula and adult were sequenced using Illumina HiSeq2000.
Project description:Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type.
Project description:Migrating schistosomula are an important stage of the schistosome lifecycle and represent a key target for elimination of infection by natural and vaccine induced host immune responses. To gain a better understanding of how these parasites initiate a primary host immune response we have characterised the host lung response to migrating Schistosoma japonicum schistosomula using a combination of histochemistry, microarrays and quantitative cytokine analysis. Our data suggest that, during a S. japonicum infection, actively migrating schistosomula induce a Type-2 cytokine response in the lung that may support the subsequent development of a CD4+ T helper 2 (Th2) response against egg antigens. This hypothesis is supported by the fact that schistosomula and schistosome eggs are known to express important Th2-inducing antigens such as omega-1, peroxiredoxin, kappa-5 and IPSE/alpha1. The host lung response to migrating schistosomula was associated with increased numbers of macrophages and expression of markers for alternatively activated macrophages (AAMφ) in the lung. Activation of AAMφ in the lung and at the systemic level could lead to the modulation of the host immune response to favour parasite survival. Induction of these cells could also contribute to diminished inflammatory responses to, for example, allergy and asthma that are known to be associated with helminth infections. These data enhance our understanding of the mechanisms whereby schistosomes may evade the immune response and the mechanisms by which schistosome infection can help influence the host response following exposure to allergenic stimuli.
Project description:In the complex lifecycle of schistosomes, four developmental stages are closely associated with their definitive hosts: cercaria (infective stage), schistosomula and adult worm (parasitic stages), egg (pathogenic- and pathophoresis-stage). We have examined the gene expression profiles of Schistosoma japonicum in the four developmental stages. Genes with different expression patterns were identified and the information obtained will help indentify new anti-schistosomal intervention targets in the future.
Project description:The life cycle of schistosomes is complex, being characterised by a series of distinct parasitic and free-living phases involving an invertebrate snail host, water and a mammalian host. A custom designed oligonucleotide microarray was utilized to profile developmental gene expression in the Asian blood fluke, Schistosoma japonicum during these parasitic and free-living transitions. Total RNAs were isolated from lung schistosomula, juvenile females and males (paired but little or no egg production), adult males and females (paired with full scale egg production), eggs, miracidia, sporocysts and cercariae. We focused on the three distinct environmental phases of the lifecycle - aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired pre-egg laying adults) and adult (paired males and females, both examined separately) stages.