The Transcriptome of Schistosoma mansoni Developing Eggs Reveals Key Mediators in Pathogenesis and Life Cycle Propagation.

Zhigang Lu,Gabriel Rinaldi,Kate A Rawlinson,Geetha Sankaranarayanan,Victoria Offord,Matthew Berriman,Paul J Brindley

doi:10.3389/fitd.2021.713123

Abstract

Schistosomiasis, the most important helminthic disease of humanity, is caused by infection with parasitic flatworms of the genus Schistosoma. The disease is driven by parasite eggs becoming trapped in host tissues, followed by inflammation and granuloma formation. Despite abundant transcriptome data for most developmental stages of the three main human-infective schistosome species-Schistosoma mansoni, S. japonicum and S. haematobium-the transcriptomic profiles of developing eggs remain under unexplored. In this study, we performed RNAseq of S. mansoni eggs laid in vitro during early and late embryogenesis, days 1-3 and 3-6 post-oviposition, respectively. Analysis of the transcriptomes identified hundreds of up-regulated genes during the later stage, including venom allergen-like (VAL) proteins, well-established host immunomodulators, and genes involved in organogenesis of the miracidium larva. In addition, the transcriptomes of the in vitro laid eggs were compared with existing publicly available RNA-seq datasets from S. mansoni eggs collected from the livers of rodent hosts. Analysis of enriched GO terms and pathway annotations revealed cell division and protein synthesis processes associated with early embryogenesis, whereas cellular metabolic processes, microtubule-based movement, and microtubule cytoskeleton organization were enriched in the later developmental time point. This is the first transcriptomic analysis of S. mansoni embryonic development, and will facilitate our understanding of infection pathogenesis, miracidial development and life cycle progression of schistosomes.

Highlights

Schistosomes are parasitic flatworms that infect more than 250 million people worldwide, mainly in Low and Middle-Income Countries [1]
To study the transcriptional profiles associated with in vitro development of eggs, we performed RNA-seq on samples corresponding to early embryogenesis, 1–3 days postoviposition (D3), and late embryogenesis, 4–6 days postoviposition (D6) (Figure 1A)
The quality of the total RNA extracted from in vitro laid eggs (IVLE) was much higher than that of the highly-degraded RNA usually obtained from eggs collected from the liver of experimentally-infected mice (Supplementary Figure S1B)

Summary

Introduction

Schistosomes are parasitic flatworms that infect more than 250 million people worldwide, mainly in Low and Middle-Income Countries [1]. It is estimated that one pair of Schistosoma mansoni adult worms can lay >300 eggs per day [4]. Once the eggs are laid by the worms in the mammalian bloodstream, about half migrate, over the course of six days, through the endothelium of blood vessels, across the epithelium of the gut and are released into the intestinal lumen [5,6,7]. The remaining eggs are swept around the body by the bloodstream and become trapped in host tissues, mainly in the liver, intestines and spleen, where they induce immune responses, severe inflammation and granuloma formation [8]. The granuloma surrounding the trapped egg consists of an immune cellular complex that includes macrophages, lymphocytes and eosinophils [3]. Fibroblasts in the granuloma produce collagen that leads to periportal fibrosis and induction of collateral circulation, including varices, which increase the risk of life-threatening haemorrhage in the digestive tract [9]

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Conclusion