Project description:Blood flukes of the genus Schistosoma (Platyhelminthes, Trematoda, Digenea) are responsible for the chronic debilitating disease schistosomiasis / bilharzia, widely considered to be second only to malaria as a global health problem and an incalculable drain on the economic development of endemic countries. Since 1994, the World Health Organization has supported a genome initiative for Schistosoma, the Schistosoma Genome Network, aimed at identifying new targets for drug and vaccine development, understanding the molecular basis of parasite metabolism and development and determining biological variation. The study of small-RNAs as key players in the regulation of gene expression differentiation is important to the understanding of the parasites biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Background Schistosomiasis is caused by parasitic blood flukes of the genus Schistosoma. Despite ongoing mass drug administration efforts, the disease remains a major public health burden in endemic regions. A better understanding of early host responses to schistosomiasis is critical for developing effective vaccines and therapeutics. Methods We conducted a longitudinal transcriptomic study of peripheral blood samples from 30 Schistosoma-naïve volunteers participating in two controlled human infection trials with male-or female-only S. mansoni cercariae. Blood was collected at six time points over 20 weeks post-infection. Whole-transcriptome RNA sequencing and integrative analyses, including differential gene expression, gene set enrichment, protein interaction networks, co-expression clustering, and immune module profiling, were employed to characterize temporal modulation of genes related to immune responses. Results Robust and highly time-dependent transcriptional responses were observed, peaking at Week 4 post-infection. Differential gene expression and pathway analyses revealed activation of immune responses, including type I and II interferon signaling, chemokine-mediated pathways, and antigen presentation. Notably, both Th1 and Th2 signatures were evident at Week 4. Key immune hubs included IFNG, TNF, and IL1B, along with transcriptional regulators such as STAT1 and IRF7. Blood transcription module analysis further highlighted transient activation of interferon and plasma cell-related responses. Conclusions This study provides a comprehensive transcriptional map of early host responses to S. mansoni infection in humans. The findings underscore the central role of interferon pathways, early mixed Th1/Th2 polarization, and inflammation-associated gene signatures in shaping host response to S. mansoni infection. These insights may inform the rational design of vaccines and biomarkers for schistosomiasis.
Project description:The aims of this study were to study ESPs to improve understanding of parasite-host interactions and to support the discovery of novel diagnostic or therapeutic targets. We used tandem mass-spectrometry to characterize the secretome of adult P. kellicotti flukes and to compare ESPs released during in vitro culture with parasite cyst fluid proteins (CFPs) which correspond to ESPs released by adult flukes in vivo. We also compared these results to the global proteome of soluble, somatic protein (SSP) extracts of whole adult flukes.
Project description:The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to repair this damage. Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite’s destructive migration, digest of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defense molecules (FhHDM). The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and anti-oxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology.
Project description:Helminth parasites secrete molecules in soluble form (i.e the secretome) or packaged into extracellular vesicles (EVs) as a means of exporting effector molecules into the host microenvironment. Once released, the parasite-derived molecules can trigger a range of biological effects including modulation of host immunity. While the secretome and molecular cargo of EVs have been characterised in many parasites, little is known about the molecules released by the rumen fluke, Calicophoron daubneyi – an emerging infection of livestock in Western Europe. Here we used a mass spectrometry-based proteomics approach to characterise the secretome of the infective newly-excysted juvenile (NEJ) stage and adult flukes. We also profile the proteome of two sub-populations of EVs (termed 15K and 120K EVs) released by the adult flukes.
Project description:This study was designed to characterize and evaluate the proteome in plasma samples collected before and after a public swim interaction involving four male (2 to 6 y) aquarium-based bottlenose dolphins (Tursiops truncatus). Blood samples were collected from the tail flukes appoximately 15 min before (n=4 samples) and 15 min after (n=4 samples) the first swim interaction of the day, which was reinforced by a regularly scheduled feeding regimen. Samples were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as conventional clinical biochemistry analysis. Mass spectra data were used to search the NCBI database restricted to Tursiops truncatus which resulted in the identification of 196 unique proteins with a broad range of functional roles based on manual GO analysis. Differential regulation of proteins was based on log2 mean fold change (FC) and statistical probability such that the abundance of lysozyme (FC -1.2036; P<0.058) an immune-related protein and flavin reductase (FC -0.9702; P<0.004) a metabolic-related protein were highest before compared to after the swim interaction. Both proteins decreased by 58 and 52%, respectively.