Abstract
BackgroundThe 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).ResultsIn 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.ConclusionsIn 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.
Highlights
The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta
Niche‐specific excretome/secretome of lumen‐ and mucosal‐dwelling fourth‐stage T. circumcincta larvae To identify niche-specific excretory–secretory (ES) proteins in lumen-dwelling (LD) and mucosal-dwelling (MD) fourth-stage T. circumcincta larvae (L4), populations of both mucosal and larval parasites were collected, from abomasa of sheep, 7 days following an oral challenge with third larval stage (L3) parasites and processed as 2 separate populations
Here, we have demonstrated the niche-specific expression of a suite of ES proteins from the fourth larval stages of T. circumcincta and demonstrated the potential of one of these proteins, Tci-Prx1, which is enriched in the ES of mucosal-dwelling as opposed to lumen-dwelling worms, to modulate the host immune response by elimination of host-derived reactive oxygen species which may be released from a range of immune effector cells to act locally to harm the parasites [26]
Summary
The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta. Host immunomodulation is multifaceted and results in polarisation of the host immune response towards a Th2 phenotype; differentiation of macrophages towards an alternative (M2) phenotype; prevention of pro-inflammatory cytokine production by dendritic cells and the production of immunoregulatory molecules and induction of regulatory T cells (recently reviewed in [4]). This regulatory activity may not be targeted at the host’s anti-helminth response but may have more general effects on the immune system. Helminth immune modulation has important implications, for the establishment of the helminth infection, and for the outcomes of concomitant conditions or infections and the efficacy of immunodiagnostics and immunoprophylactic approaches (e.g. see [5])
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