Schistosoma mansoni venom allergen-like protein 6 (SmVAL6) maintains tegumental barrier function

Perally, Samïrah; Geyer, Kathrin K.; Farani, Priscila Silva Grijó; Chalmers, Iain W.; Fernández-Fuentes, Narcís; Maskell, Daniel R.; Hulme, Benjamin J.; Forde-Thomas, Josephine; Phillips, Dylan; Farias, Leonardo P.; Collins, James J.; Hoffmann, Karl F.

doi:10.1016/j.ijpara.2020.09.004

Cited by 6 publications

(4 citation statements)

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“…The role of Sm VALs is not yet confirmed, but in some nematodes, VALs are involved in mechanisms of infection establishment and host immunomodulation ( 53 ). More recently, using a combination of RNAi and in situ hybridisation, Perally and colleagues demonstrated the critical role of Sm VAL6 in the maintenance of the tegumental barrier in adult worms ( 54 ). These findings suggest that the Sm VALs may be tentative targets for drug development.…”

Section: Discussionmentioning

confidence: 99%

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

Sankaranarayanan

Rawlinson

et al. 2021

Front. Trop. Dis

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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.

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Section: Discussionmentioning

confidence: 99%

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

Sankaranarayanan

Rawlinson

et al. 2021

Front. Trop. Dis

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“…Growth delay leading to a lack of adequate resistance of the worm to host clearance may be a significant factor in worm mortality. The SPC25 was significantly overexpressed in the tegument of male worms, and S. japonicum tegument changes are the primary adaptative mechanism for escaping the host's immune response in several studies (Abath and Werkhauser, 1996;Castro-Borges et al, 2011;Sotillo et al, 2015;Perally et al, 2021). Thus, for the RNAi-treated schistosomula, the inability to settle down might be linked to their immature tegument at 30 dpi (Brouwers et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum

Yang

Luo²,

Zhang³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundSchistosomiasis, the second most neglected tropical disease defined by the WHO, is a significant zoonotic parasitic disease infecting approximately 250 million people globally. This debilitating disease has seriously threatened public health, while only one drug, praziquantel, is used to control it. Because of this, it highlights the significance of identifying more satisfactory target genes for drug development. Protein translocation into the endoplasmic reticulum (ER) is vital to the subsequent localization of secretory and transmembrane proteins. The signal peptidase complex (SPC) is an essential component of the translocation machinery and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. Inhibiting the expression of SPC can lead to the abolishment or weaker cleavage of the signal peptide, and the accumulation of uncleaved protein in the ER would affect the survival of organisms. Despite the evident importance of SPC, in vivo studies exploring its function have yet to be reported in S. japonicum.MethodsThe S. japonicum SPC consists of four proteins: SPC12, SPC18, SPC22 and SPC25. RNA interference was used to investigate the impact of SPC components on schistosome growth and development in vivo. qPCR and in situ hybridization were applied to localize the SPC25 expression. Mayer’s carmalum and Fast Blue B staining were used to observe morphological changes in the reproductive organs of dsRNA-treated worms. The effect of inhibitor treatment on the worm’s viability and pairing was also examined in vitro.ResultsOur results showed that RNAi-SPC delayed the worm's normal development and was even lethal for schistosomula in vivo. Among them, the expression of SPC25 was significantly higher in the developmental stages of the reproductive organs in schistosomes. Moreover, SPC25 possessed high expression in the worm tegument, testes of male worms and the ovaries and vitellarium of female worms. The SPC25 knockdown led to the degeneration of reproductive organs, such as the ovaries and vitellarium of female worms. The SPC25 exhaustion also reduced egg production while reducing the pathological damage of the eggs to the host. Additionally, the SPC-related inhibitor AEBSF or suppressing the expression of SPC25 also impacted cultured worms’ pairing and viability in vitro.ConclusionsThese data demonstrate that SPC is necessary to maintain the development and reproduction of S. japonicum. This research provides a promising anti-schistosomiasis drug target and discovers a new perspective on preventing worm fecundity and maturation.

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“…VALs have garnered significant attention in the study of parasitic helminths. Although their exact functions remain elusive, there is evidence suggesting that they may be involved in tissue migration [ 42 , 43 ], immunomodulation [ 44 ], and even structural functions [ 45 ]. However, recent research has contested conventional perspectives by characterizing egg-specific VALs as "larval transformation proteins".…”

Section: Discussionmentioning

confidence: 99%

Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity

Peterková,

Konečný,

Macháček

et al. 2024

PLoS Pathog

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The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg “winners” attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg “losers” carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped “losers” instead of migrating intestinal “winners”. This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite’s eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.

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Schistosoma mansoni venom allergen-like protein 6 (SmVAL6) maintains tegumental barrier function

Abstract: Graphical abstract

Cited by 6 publications

References 58 publications

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

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

Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum

Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity

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