Characterisation of a niche-specific excretory-secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta. 2019

Daniel R G Price, and Alasdair J Nisbet, and David Frew, and Yvonne Bartley, and E Margaret Oliver, and Kevin McLean, and Neil F Inglis, and Eleanor Watson, and Yolanda Corripio-Miyar, and Tom N McNeilly
Moredun Research Institute, Pentlands Science Park, Edinburgh, EH26 0PZ, UK. daniel.price@moredun.ac.uk.

BACKGROUND The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta. Host immunity to this parasite is slow to develop, consistent with the ability of T. circumcincta to suppress the host immune response. Previous studies have shown that infective fourth-stage T. circumcincta larvae produce excretory-secretory products that are able to modulate the host immune response. The objective of this study was to identify immune modulatory excretory-secretory proteins from populations of fourth-stage T. circumcincta larvae present in two different host-niches: those associated with the gastric glands (mucosal-dwelling larvae) and those either loosely associated with the mucosa or free-living in the lumen (lumen-dwelling larvae). RESULTS In this study excretory-secretory proteins from mucosal-dwelling and lumen-dwelling T. circumcincta fourth stage larvae were analysed using comparative 2-dimensional gel electrophoresis. A total of 17 proteins were identified as differentially expressed, with 14 proteins unique to, or enriched in, the excretory-secretory proteins of mucosal-dwelling larvae. One of the identified proteins, unique to mucosal-dwelling larvae, was a putative peroxiredoxin (T. circumcincta peroxiredoxin 1, Tci-Prx1). Peroxiredoxin orthologs from the trematode parasites Schistosoma mansoni and Fasciola hepatica have previously been shown to alternatively activate macrophages and play a key role in promoting parasite induced Th2 type immunity. Here we demonstrate that Tci-Prx1 is expressed in all infective T. circumcincta life-stages and, when produced as a recombinant protein, has peroxidase activity, whereby hydrogen peroxide (H2O2) is reduced and detoxified. Furthermore, we use an in vitro macrophage stimulation assay to demonstrate that, unlike peroxiredoxins from trematode parasites Schistosoma mansoni and Fasciola hepatica, Tci-Prx1 is unable to alternatively activate murine macrophage cells. CONCLUSIONS In this study, we identified differences in the excretory-secretory proteome of mucosal-dwelling and lumen-dwelling infective fourth-stage T. circumcincta larvae, and demonstrated the utility of this comparative proteomic approach to identify excretory-secretory proteins of potential importance for parasite survival and/or host immune modulation.

UI MeSH Term Description Entries
D007411 Intestinal Diseases, Parasitic Infections of the INTESTINES with PARASITES, commonly involving PARASITIC WORMS. Infections with roundworms (NEMATODE INFECTIONS) and tapeworms (CESTODE INFECTIONS) are also known as HELMINTHIASIS. Parasitic Intestinal Diseases,Disease, Parasitic Intestinal,Diseases, Parasitic Intestinal,Intestinal Disease, Parasitic,Parasitic Intestinal Disease
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D009092 Mucous Membrane An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa. Lamina Propria,Mucosa,Mucosal Tissue,Muscularis Mucosae,Mucous Membranes,Membrane, Mucous,Membranes, Mucous,Mucosae, Muscularis,Mucosal Tissues,Propria, Lamina,Tissue, Mucosal,Tissues, Mucosal
D006790 Host-Parasite Interactions The relationship between an invertebrate and another organism (the host), one of which lives at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically. Host-Parasite Relations,Parasite-Host Relations,Host-Parasite Relationship,Parasite-Host Interactions,Host Parasite Interactions,Host Parasite Relations,Host Parasite Relationship,Host-Parasite Interaction,Host-Parasite Relation,Host-Parasite Relationships,Interaction, Host-Parasite,Interaction, Parasite-Host,Interactions, Host-Parasite,Interactions, Parasite-Host,Parasite Host Interactions,Parasite Host Relations,Parasite-Host Interaction,Parasite-Host Relation,Relation, Host-Parasite,Relation, Parasite-Host,Relations, Host-Parasite,Relations, Parasite-Host,Relationship, Host-Parasite,Relationships, Host-Parasite
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D012757 Sheep Diseases Diseases of domestic and mountain sheep of the genus Ovis. Ovine Diseases,Disease, Ovine,Disease, Sheep,Diseases, Ovine,Diseases, Sheep,Ovine Disease,Sheep Disease
D014251 Trichostrongyloidea A superfamily of nematodes. Most are intestinal parasites of ruminants and accidentally in humans. This superfamily includes seven genera: DICTYOCAULUS; HAEMONCHUS; Cooperia, OSTERTAGIA; Nematodirus, TRICHOSTRONGYLUS; and Hyostrongylus. Trichostrongyloideas
D015180 Electrophoresis, Gel, Two-Dimensional Electrophoresis in which a second perpendicular electrophoretic transport is performed on the separate components resulting from the first electrophoresis. This technique is usually performed on polyacrylamide gels. Gel Electrophoresis, Two-Dimensional,Polyacrylamide Gel Electrophoresis, Two-Dimensional,2-D Gel Electrophoresis,2-D Polyacrylamide Gel Electrophoresis,2D Gel Electrophoresis,2D PAGE,2D Polyacrylamide Gel Electrophoresis,Electrophoresis, Gel, 2-D,Electrophoresis, Gel, 2D,Electrophoresis, Gel, Two Dimensional,Polyacrylamide Gel Electrophoresis, 2-D,Polyacrylamide Gel Electrophoresis, 2D,Two Dimensional Gel Electrophoresis,2 D Gel Electrophoresis,2 D Polyacrylamide Gel Electrophoresis,Electrophoresis, 2-D Gel,Electrophoresis, 2D Gel,Electrophoresis, Two-Dimensional Gel,Gel Electrophoresis, 2-D,Gel Electrophoresis, 2D,Gel Electrophoresis, Two Dimensional,PAGE, 2D,Polyacrylamide Gel Electrophoresis, 2 D,Polyacrylamide Gel Electrophoresis, Two Dimensional,Two-Dimensional Gel Electrophoresis

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