Abstract
Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.
Highlights
Epidemiological data suggest that more than one billion people worldwide, as well as numerous groups of livestock, are infected with at least one species of gastrointestinal (GI) nematode [1]
Western blot analysis revealed that rat anti-H. contortus ES proteins (HcESPs) IgG (Figure 1A, lane 2) recognized all the bands of natural HcESPs distributed from ~10 kD to ~180 kD, but the control normal rat IgG (Figure 1A, lane 3) did not recognize any band, indicating that the rat anti-HcESP IgG was specific to the HcESPs
HcESPs affected cell viability and induced cell apoptosis To verify the new clues from Gene Ontology (GO) annotation indicating that HcESP stimuli might affect T cell growth and survival, we further investigated the biological effects of HcESPs on the viability of goat T cells
Summary
Epidemiological data suggest that more than one billion people worldwide, as well as numerous groups of livestock, are infected with at least one species of gastrointestinal (GI) nematode [1]. These parasitic species have evolved sophisticated and highly integrated mechanisms to reside in the GI tract of the hosts [2]. The barber’s pole worm, Haemonchus contortus, is a voraciously blood-feeding and highly pathogenic GI nematode inhabiting the abomasum of small ruminants (mainly sheep and goats) [6]. H. contortus is transmitted via a complex life cycle involving three
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