Authors

Z Ibnahaten¹; N Muller-Sienerth²; C Crosnier³;  ¹ University of York, UK;  ² Wellcome Sanger Institute, UK;  ³ Department of Biology, University of York, UK

Discussion

Schistosomiasis is a parasitic neglected tropical disease affecting over 240 million people annually, primarily in low to middle income countries. One of the main species of Schistosoma responsible for the disease is Schistosoma mansoni which is transmitted through infected water. Praziquantel is at present the only drug that effectively kills adult parasites, and no licenced vaccine is currently available. To survive within the vasculature, schistosomes must interact with their host and extracellular parasite antigens are likely to be involved in these interactions. Micro-exon genes (MEGs) encode for secreted and cell surface protein families, where symmetrical micro-exons (from 6bp up to 81bp) are present in the coding sequence and can give rise to multiple protein isoforms through exon skipping. MEGs also exhibit high non-synonymous/synonymous substitution rates and possibly play a role in immune evasion through alternative splicing and antigenic variation. S.mansoni lacking the oesophageal gland (a MEG upregulation hotspot) cannot establish infection in immunosuppressed mice, so it is strongly theorised that the MEGs expressed at the oesophagus play a role in immune evasion or suppression. Our aim is to characterise the role of S.mansoni MEG proteins during mammalian infection. In a first instance, we will aim to identify the MEG transcripts variants expressed at different life stages of the parasite’s life cycle through long read RNA sequencing. These MEGs will then be expressed recombinantly in mammalian cells and tested against a library of human immune receptors using SAVEXIS to identify new host:parasite interactions. The function of these interactions will then be tested in cellular assays and possibly in a murine model of S. mansoni infection.