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:Microtus fortis (M. fortis) is the only mammal in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented, resulting in the failure of the parasite to mature and complete its life cycle. MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs, has been found to introduce a whole new layer of gene regulation in eukaryotes. The anti-schistosomiasis mechanosm of M. fortis may require the participation of miRNA-mediated gene expression. In the present study, the difference pathological change of different tissue such as liver, spleen and lung of M. fortis were observed by using haematoxylin-eosin staining. Also, the miRNA expression in different tissue of M. fortis and mice before challenge and 10 days post-infection with schistosomes were first compared using microRNA microarray analysis. Histological analyses showed that S. japonicum infection in M. fortis resulted in more intensive inflammatory response and pathologic change than mice. The microarray investigations showed that 388 miRNAs detected common expressed in the two species, and 11 miRNAs in liver, 25 miRNAs in spleen and 28 miRNAs in lung differentially expressed in non-permissive M. fortis while increased, decreased or nearly fixed in mice. Further studies of the differentially expressed miRNAs demonstrated that many important signal pathway were triggered after the S. japonicum infection in M. fortis rather than the mouse, such as the metabolism of some nutrient material such as fatty-acid, cholesterol, lipid, insulin, and carbohydrate; immune response such as B and T cell differentiation, monocyte differentiation, the inflammation, NF-kappaB binding, even the in innate immune system; Cell differentiation and apoptosis such as erythrocytic differentiation and targeting proapoptotic and antiapoptotic proteins. These results may provide new insights into general mechanisms of regulation in non-permissive M. fortis, exploit the potential miRNA regulatory networks and the interaction between parasites and different hosts, which provide valuable new information on schistosome biology and valuable information for the better understanding of schistosome development and host-parasite interactions. We collected liver, spleen and lung from control and 10 days post-infection with schistosomes of M. fortis, mice and rat, respectively.
Project description:Microtus fortis (M. fortis) is the only mammal in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented, resulting in the failure of the parasite to mature and complete its life cycle. MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs, has been found to introduce a whole new layer of gene regulation in eukaryotes. The anti-schistosomiasis mechanosm of M. fortis may require the participation of miRNA-mediated gene expression. In the present study, the difference pathological change of different tissue such as liver, spleen and lung of M. fortis were observed by using haematoxylin-eosin staining. Also, the miRNA expression in different tissue of M. fortis and mice before challenge and 10 days post-infection with schistosomes were first compared using microRNA microarray analysis. Histological analyses showed that S. japonicum infection in M. fortis resulted in more intensive inflammatory response and pathologic change than mice. The microarray investigations showed that 388 miRNAs detected common expressed in the two species, and 11 miRNAs in liver, 25 miRNAs in spleen and 28 miRNAs in lung differentially expressed in non-permissive M. fortis while increased, decreased or nearly fixed in mice. Further studies of the differentially expressed miRNAs demonstrated that many important signal pathway were triggered after the S. japonicum infection in M. fortis rather than the mouse, such as the metabolism of some nutrient material such as fatty-acid, cholesterol, lipid, insulin, and carbohydrate; immune response such as B and T cell differentiation, monocyte differentiation, the inflammation, NF-kappaB binding, even the in innate immune system; Cell differentiation and apoptosis such as erythrocytic differentiation and targeting proapoptotic and antiapoptotic proteins. These results may provide new insights into general mechanisms of regulation in non-permissive M. fortis, exploit the potential miRNA regulatory networks and the interaction between parasites and different hosts, which provide valuable new information on schistosome biology and valuable information for the better understanding of schistosome development and host-parasite interactions.
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.