A Divergent Member of the Transforming Growth Factor β Receptor Family from Schistosoma mansoni Is Expressed on the Parasite Surface Membrane

Abstract

To optimize reproductive success under the limitations determined by conditions within an individual host, parasitic helminths have evolved mechanisms that allow them to detect and respond to host factors such as species, age, sex, reproductive condition, and immune status. Using the model helminth Schistosoma mansoni, we have explored the possibility that parasitic helminths express signal-transducing receptor molecules on their surfaces. Here, we present the identification of a schistosome member of the transforming growth factor ␤ receptor family of cell-surface receptors, the first member of this family to be identified in a platyhelminth. The putative protein kinase domain of the schistosome receptor displays up to 58% amino acid identity to kinase domains of other type I receptor serine-threonine kinases, and contains a potential "GS domain," suggesting it is a divergent member of the type I receptor subfamily. This receptor is expressed on the surface of the parasite's syncytial tegument and expression of receptor messenger RNA and protein is up-regulated following infection of the mammalian host. The receptor protein can be isolated in a phosphorylated form from adult parasites, which together with its surface location, suggests that it functions in transducing signals across the parasite surface membrane.An estimated 200 million people throughout tropical and temperate regions of the world are infected with parasitic trematodes of the genus Schistosoma (1). These parasites possess complex life cycles, using humans and other mammals as definitive hosts, while various species of aquatic snails serve as intermediate hosts for larval stages. After infection of the definitive host by infectious stage cercariae of Schistosoma mansoni, the immature parasites undergo a complex program of development to become sexually mature adult males and females at approximately 6 weeks post-infection. During development, the parasites migrate from their point of entry in the skin to the circulatory system and then pass via the heart and lungs to their final destination in the mesenteric veins of the hepatic portal circulation. The severe hepatic and intestinal pathology associated with schistosomiasis is caused by the vigorous host immune response to large quantities of schistosome eggs produced by pairs of adult parasites residing in the mesenteric veins.Previous studies have suggested that successful completion of schistosome development and migration is dependent on the receipt of appropriate host-derived signals by the parasite, and on transmission of signals between male and female parasites (2-5). Since the schistosome surface is composed of a continuous cytoplasmic tegument bound externally by a lipid bilayer, we hypothesized that schistosomes may possess surface-exposed, membrane-bound receptor proteins that allow signals in the surrounding milieu to be detected. To test this hypothesis, we developed a procedure to specifically label surface proteins expressed on the outer membrane of the parasite tegument using a p...

The Lophotrochozoan TGF-β signalling cassette - diversification and conservation in a key signalling pathway

“…Schistosome receptor complements have been studied elsewhere in depth (Davies et al, 1998, Forrester et al, 2004, and in many ways their complements represent a surprising finding, given the presence in S. mansoni of only two TGF-b-like ligands. These complements do not map exactly onto the canonical cassette, but, as hypothesised in Osman et al, (2006) and earlier in this manuscript, their quantity, when compared to the few ligands encoded in its genome, may suggest that these molecules respond to host, rather than endogenous, signalling cues.…”

Helminth Infection and Type 1 Diabetes

“…These findings are mirrored in the human clinical setting, where studies of HIVpositive patients in regions endemic for S. mansoni revealed that fecal egg counts, but not infection intensity, were negatively correlated with CD4 + T cell counts [23]. Further supporting the coevolution of S. mansoni with the mammalian immune system, evidence exists that adult worms can sense the human regulatory cytokine, transforming growth factor beta (TGF-β), and that stimulation with TGF-β induces expression of genes linked to sexual maturation and malefemale interaction and may modulate embryonic development [24][25][26][27]. S. mansoni has thus evolved not only to detect mediators of host immunity, but also to use these signals in its own program of maturation and reproduction.…”

Growth factor receptors in helminth parasites: Signalling and host–parasite relationships

“…1) and shown to be expressed at the surface of the parasite following its entry into the mammalian host [13]. Using a heterologous expression system, SmTbR1 was shown to interact with human TbRII and to activate Smad2 signalling molecules in response to human TGF-b [14].…”