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:Genome-wide transcriptional survey in peripheral blood mononuclear cells (PBMCs) by RNA-Seq in schoolchildren living in an endemic area in Gabon, with and without Schistosoma haematobium infection before and after treatment with the anthelminthic drug praziquantel.
Project description:Genome-wide transcriptional survey in peripheral blood mononuclear cells (PBMCs) by RNA-Seq in schoolchildren living in an endemic area in Gabon, with and without Schistosoma haematobium infection before and after treatment with the anthelminthic drug praziquantel.
Project description:Background: Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population, and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. Methodology: A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. Results: A total of 1306 proteins and 8752 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). Conclusion: These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.
Project description:Schistosomiasis increases the risk of HIV acquisition in women, by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or S. mansoni infection using mucosal gene expression and cervicovaginal lavage cytokine levels. We recruited women with/without S. haematobium and with/without S. mansoni infections from separate villages in rural Tanzania, as determined by urine and stool microscopy and serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. In the S. haematobium village, 110 genes were differentially expressed in the cervical mucosa of women with (n=18) versus without (n=39) S. haematobium. Among the 27 cytokines analyzed in cervicovaginal lavage fluids, interleukin 15 (IL-15) was lower in women with S. haematobium (62.8 versus 102.9 pg/mL, adjusted p=0.0013). Differences were not observed in the S. mansoni setting between women with (n=11) or without (n=29) S. mansoni. We demonstrate altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni, which may impact HIV acquisition and cancer risks. Studies to determine effects of anti-schistosome treatment on these mucosal alterations are needed.
Project description:Schistosome worms infect over 200 million people worldwide. They live in the host’s bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active Schistosoma haematobium infection and to determine whether this signature differs between males and females. mRNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis (IPA) was used to identify gene networks altered in the presence of S. haematobium. We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially expressed genes between those with or without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with 1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. The top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of schistosome infection.