ABSTRACT: Study on differences in the pathology, T cell subsets and gene expression in susceptible and non-susceptible hosts infected with Schistosoma japonicum
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: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.
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.
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:Chinese and Philippine strains of the blood fluke Schistosoma japonicum present clear and distinctive phenotypes in areas of fecundity, pathology, drug sensitivity and immunology. Despite these differences large scale sequencing efforts have focused solely on Chinese mainland strain of the parasite. We have undertaken a comparative genomic hybridisation (CGH) approach to highlight some of the structural differences in the genome of two of the major geographical isolates of S. japonicum. We identified seven distinct regions of the S. japonicum genome that present differential CGH between Chinese and Philippine strains of the blood fluke Schistosoma japonicum, representing either deletion or duplication regions in the Philippine strain. Within these regions, genes that may be related to phenotypical differences are identified and discussed. Genomic DNA was isolated from adult (7 week post cercarial challenge) Schistosoma japonicum Chinese and Philippine isolates and separate maleand femalesamples comparatively hybridised on an Agilent customn designed oligo microarray.
Project description:Chinese and Philippine strains of the blood fluke Schistosoma japonicum present clear and distinctive phenotypes in areas of fecundity, pathology, drug sensitivity and immunology. Despite these differences large scale sequencing efforts have focused solely on Chinese mainland strain of the parasite. We have undertaken a comparative genomic hybridisation (CGH) approach to highlight some of the structural differences in the genome of two of the major geographical isolates of S. japonicum. We identified seven distinct regions of the S. japonicum genome that present differential CGH between Chinese and Philippine strains of the blood fluke Schistosoma japonicum, representing either deletion or duplication regions in the Philippine strain. Within these regions, genes that may be related to phenotypical differences are identified and discussed.
Project description:To date, 115 miRNAs genes (precursors) have been registered in miRBase for Schistosoma mansoni, and 56 for Schistosoma japonicum (225 and 79 mature miRNA, respectively). miRNAs have not been systematically described in Schistosoma haematobium. Our aim in this study was to systematically characterize and quantify miRNA in Schistosoma by species, developmental stage and sex and to test the usefulness of this characterization in biomarker discovery for infection. We found read evidence for the expression of 65/225 (36 precursors) known S. mansoni miRNA and 76/79 (55 precursors) of the known S. japonicum miRNA. We report a handful of novel miRNA in each of these species and provide a curated list of S. haematobium miRNA. We report differences of miRNA expression by species, sex and developmental stages. Lastly, we present preliminary results of miRNA deep sequencing from infected specimens (mouse and human).
Project description:Macrophages initiate, modulate, and also serve as final effector cells in immune responses during course of schistosomal infections. Presently, we discussed the roles of the gene expression profile and functional changes of macrophages in immune responses against the Schistosoma japonicum by microarray experiments. Hierarchical clustering analysis demonstrated that a significant switch in gene transformation associated with a type-1 response and linked with a type-2 cytokine phenotype occurs between 4.5 and 8 weeks post-infection. Moreover, the gene profiles at 3 later time-points following egg challenge were similar in complexity and magnitude. These data also showed that there are mostly inhibition in gene expression related TLR, IFN, MHC and TNFrsf at the switch between 4.5 and 8 weeks post-infection, It is suggested that these immunomodulatory genes may be down-regulated in resistance against S. japonicum eggs and granuloma pathology. The induction of alternatively activated macrophage was important for dampening the inflammation in hepatic granulomas and contributing to a decrease in cytotoxicity. The genes expressions involved in repair/remodeling during liver fibrosis were also observed after eggs production. Understanding these immune mechanisms related to parasite resistance, pathology, and growth with regard to the disease will be helpful in further studies on S. japonicum. Two-condition experiment, Control mice vs. Schistosoma japonicum-infected mice. replicates: 2 infected replicates. Different post-infection weeks
Project description:Schistosome parasites lay up to a thousand eggs per day inside the veins of their mammalian hosts. The immature eggs deposited by females against endothelia of venules will embryonate within days. Approximately 30% of the eggs will migrate to the lumen of the intestine to continue the parasite life cycle. Many eggs, however, are trapped in the liver and intestine causing the main pathology associated with schistosomiasis mansoni and japonica, the liver granulomatous response. Excretory/Secretory egg proteins drive much of egg-induced pathogenesis of schistosomiasis mansoni, and Schistosoma japonicum induce a markedly distinct granulomatous response to that of S. mansoni.
Project description:Rats and mice were infected with Schistosoma japonicum, and the worms were collected from infected rats and mice. Worms in rats were exposed to high level of NO, while the worms in mice were not. Then a S-nitrosocysteine proteomics of Schistosoma japonicum collected from infected rats and mice was performed and the data were collected.