Abstract
Haemonchus contortus (H. contortus) has evolved sophisticated evasion mechanisms to ensure their survival, including generating excretion and secretion products (ESPs) to regulate the secretion of host cytokines. Interleukin 4 (IL4) is a classic T-helper cell type 2 (Th2)-type cytokine that plays an irreplaceable role against nematode infection. In this study, three proteins, glutathione S-transferase domain containing protein (HcGST), transthyretin domain containing protein (HcTTR) and calponin actin-binding domain containing protein (HcCab), were identified to bind to goat IL4 by co-immunoprecipitation (Co-IP) assays and yeast two-hybrid screening. Additionally, cell proliferation analysis showed that HcTTR blocked the IL4-induced proliferation of peripheral blood mononuclear cells in goats, while HcGST and HcCab did not. In addition, HcTTR could also downregulate the transcription of candidate genes in the IL4-induced JAK/STAT pathway. These results indicated that HcTTR is a novel antagonist against goat IL4 from HcESPs, and this information could improve our understanding of the relationship between host cytokines and parasite infections.
Highlights
Parasitic nematodes have evolved complex mechanisms to participate in host immunomodulatory and to evade host immune surveillance
The results demonstrated that rHcTTR treatments significantly suppressed the proliferation of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner compared with the effects observed for the positive control group (ANOVA, F (8, 18) = 17.8, P < 0.0001) (Figure 4A)
Interleukin 4 (IL4) is regarded as a prominent feature of the T-helper cell type 2 (Th2)-dominated immune response and plays an important role in preventing parasitic nematode infection
Summary
Parasitic nematodes have evolved complex mechanisms to participate in host immunomodulatory and to evade host immune surveillance. During infection, these organisms have not warded off the host immune attack; but rather, nematodes interfere with, direct and modulate immune responses in favor of their own survival. Nematodes have evolved immunosuppressive or immunomodulatory molecules to influence the function of cytokines, which can play an important role in protecting the host from infection of pathogens including parasites [1]. A non-homologous molecule, TGF-β mimic (Hp-TGM), Cytokine IL4 is a regulator of the adaptive immune response, which plays a critical role in the type 2 immune response against Haemonchus contortus infection [6]. The significant reduction in fecal egg counts (FECs) was associated with the secretion of IL4 in the serum of infected sheep [8]
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