Project description:We report on the small RNA profiles of Schistosoma japonicum (S. japonicum) miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production.
Project description:We report on the small RNA profiles of Schistosoma japonicum (S. japonicum) miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. Examination of different miRNAs between males and females in Schistosoma japonicum
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:Alternatively activated macrophages (AAMφs) play important roles in a number of Th2 driven pathologies including asthma and allergy, and a number of parasitic infections. Our studies, and those of others, investigating the pathologies associated with infection with the helminth Schistosoma japonicum implicate a role for AAMφs in fibrosis and immunomodulation.. In the present study we show that S. japonicum-secreted egg antigens are able to induce the alternative activation of macrophages as characterised by the induction of Chi3l3 and Arg1 expression. Retnla, another common marker of AAMφs, was not consistently induced in these macrophages suggesting that the specific function of these cells may differ to those induced by S. mansoni and other parasites. Closer examination of the gene expression profile and functionality of these cells identified pathways independent of Retnla expression that could be important for their immunomodulatory activity such as modulating expression of T-cell co-stimulatory molecules and chemokines. In vivo generated S. japonicum soluble egg antigen stimulated AAMφs also exhibited a reduction in their phagocytic ability likely related to the induction of IL4 and decreased expression of cell surface receptors. Additionally these macrophages exhibited reduced expression of Toll-like receptors (TLRs) and an associated reduction in responsiveness to stimulation with TLR ligands. We did not observe pathways that would suggest that AAMφs have a direct profibrotic activity. Taken together, these data describe a mechanism by which alternative activation of macrophages may be induced during S. japonicum infection and highlight the importance of the context of activation in directing AAMφ phenotype and function. The gene expression profile of Schistosoma japonicum soluble egg antigen (SEA)-stimulated macrophages was compared with that of PBS stimulated controls. Macrophages were isolated from the peritoneal cavity of BALB/c mice (n=6 per group) stimulated by intraperitoneal injection with SEA or PBS. The macrophages were pooled and RNA was extracted from these cells. Microarray analysis was performed on cRNA synthesised from total RNA derived from these macrophages. The experiment was performed twice creating two biological replicates. Fold-change (relative to the respective PBS control) reported in supplementary file linked below.
Project description:Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the molecular differences associated with rapid progression to schistosomiasis in cirrhotic patients. Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Results: On the basis of our analysis, we identified 1,144 proteins, among which 66 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection. Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. C1QA and CFD are potentially diagnostic markers for patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.
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 severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the mammalian host immune response. The local cellular and molecular mechanisms that co-ordinate hepatic granuloma formation during schistosome infection are still poorly understood. We used a combination of laser microdissection microscopy and microarray analysis to further our understanding of fibrogenesis and granuloma formation in C57BL/6 mice infected with Schistosoma japonicum. We compared hepatic gene expression profiles in histologically distinct zones both within, and directly proximal to, granulomas during the course of their development.