Transcriptome of the parasitic flatwormSchistosoma mansoniduring intra-mammalian development

Abstract

<jats:title>Abstract</jats:title><jats:p>Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of <jats:italic>Schistosoma mansoni</jats:italic>. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of <jats:italic>in vivo</jats:italic> intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host–parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.</jats:p><jats:sec><jats:title>Author Summary</jats:title><jats:p>The life cycle of the parasitic flatworm <jats:italic>Schistosoma mansoni</jats:italic> is split between snail and mammalian (often human) hosts. An infection can last for more than 10 years, during which time the parasite physically interacts with its mammalian host as it moves through the bloodstream, travelling through the lungs and liver, to eventually establish a chronic infection in the blood vessels around the host gut. Throughout this complex journey, the parasite develops from a relatively simple larval form into a more complex, sexually reproducing adult. To understand the molecular basis of parasite interactions with the host during this complex journey we have produced genome-wide expression data from developing parasites. The parasites were collected from experimentally-infected mice over its developmental time-course from the poorly studied lung stage, to the fully mature egg-laying adult worm. The data highlight many genes involved in processes known to be associated with key stages of the infection. In addition, the gene expression data provide a unique view of interactions between the parasite and the immune system in the lung, including novel players in host-parasite interactions. A detailed understanding of these processes may provide new opportunities to design intervention strategies, particularly those focussed on the early stages of the infection that are not targeted by current chemotherapy.</jats:p></jats:sec>

Dynamic Expression of Long Non-Coding RNAs Throughout Parasite Sexual and Neural Maturation in Schistosoma Japonicum

“…In this respect, it is known that the parasites pass through considerable changes in different tissues after entering the host, including in the nervous system [24], with some of these changes driven by stem cells in the schistosomula stage (first two weeks of infection) [25,26]. In S. mansoni, it was recently demonstrated that protein-coding genes associated with embryogenesis, neuronal development, brain development, and cell-fate differentiation, such as SOX, procadherin family, Wnt and frizzled receptors, have the highest expression in the sixth day post-infection, followed by a steady decline towards the adult stage [27]. In S. japonicum, the ortholog protein-coding genes were all present in the turquoise module: SOX, EWB00_011227 (mRNA16657); procharedin family, EWB00_002205 (mRNA3141), EWB00_00339 (mRNA4912), EWB00_009292 (mRNA13839); Wnt, EWB00_009528 (mRNA14229); frizzled receptor, EWB00_011205 (mRNA16607 and mRNA16608).…”

Large CRISPR-Cas-induced deletions in the oxamniquine resistance locus of the human parasite Schistosoma mansoni

“…High-throughput datasets, including high quality reference genomes for the three main species of schistosomes [5][6][7], have been generated. More recently, a thorough transcriptome analysis during the parasite's intra-mammalian development [8], and the identification of different cell types by single-cell RNA sequencing of various life cycle stages [9,10] represent significant steps towards deciphering cell fate and pathways involved in parasite development and host-parasite interactions.…”

Assembled chromosomes of the blood fluke Schistosoma mansoni provide insight into the evolution of its ZW sex-determination system

“…Adult worms were collected by portal perfusion from experimentally-infected mice at 6, 13, 17, 21, 28 and 35 days post infection following methods previously described [66]. Clonal female or male adult worms were collected from mice infected with PCR-confirmed female or male cercariae, respectively, shed from single monomiracium-infected snails.…”