Abstract
BackgroundHepatocellular carcinoma-associated antigen 59 (HCA59), which is one of the most important excretory/secretory products of Haemonchus contortus (HcESPs), is known to have antigenic functions. However, its immunomodulatory effects on host cells are poorly understood.MethodsHere, we cloned the HCA59 gene and expressed the recombinant protein of HCA59 (rHCA59). Binding activities of rHCA59 to goat peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were checked by immunofluorescence assay (IFA) and the immunoregulatory effects of rHCA59 on cytokine secretions, cell migration, cell proliferation, nitric oxide production, and changes in expression of genes in related pathways were observed by co-incubation of rHCA59 with goat PBMCs and DCs. Monocyte phagocytosis and characterization of goat blood DC subsets were detected by flow cytometry.ResultsThe IFA results revealed that rHCA59 could bind to PBMCs and DCs. Treatment of PBMCs with rHCA59 significantly increased cellular proliferation and NO production in a dose–dependent manner, while cell migration was vigorously blocked. Treatment with rHCA59 significantly suppressed monocytes phagocytosis. The quantity of surface marker CD80 on DCs increased significantly after rHCA59 treatment. In addition, the expression of genes included in the WNT pathway was related to the differentiation and maturation of DCs, and the production of IL-10 and IL-17 produced by PBMCs was altered.ConclusionsOur findings illustrated that rHCA59 could enhance host immune responses by regulating the functions of goat PBMCs and DCs, which would benefit our understanding of HCA59 from parasitic nematodes contributing to the mechanism of parasitic immune evasion.
Highlights
Hepatocellular carcinoma-associated antigen 59 (HCA59), which is one of the most important excretory/secretory products of Haemonchus contortus (HcESPs), is known to have antigenic functions
The results showed that β-catenin and DVL presented significantly elevated expression when cells were incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF)+interleukin 4 (IL-4)+LPS
The results showed that recombinant protein of HCA59 (rHCA59) significantly increased the secretions of interleukin 17 (IL-17) and interleukin 10 (IL-10) of goat peripheral blood mononuclear cells (PBMC), but had no effect on the other cytokine the total ESP of this nematode were shown to increase the production of IL-17 or IL-10 [26, 47,48,49]
Summary
Hepatocellular carcinoma-associated antigen 59 (HCA59), which is one of the most important excretory/secretory products of Haemonchus contortus (HcESPs), is known to have antigenic functions. Haemonchus species are the most important blood-sucking nematodes of domestic animals in sub-tropical and tropical areas worldwide. Infections of these parasites usually appear in young animals and resistance to infection develops with exposure in adult hosts [1]. Hepatocellular carcinoma-associated antigen 59 (HCA59), which is a component of the excretory/secretory products of H. contortus (HcESPs), can be isolated from different larval stages of this nematode [10]. In NCBI, HCA59 had 1111 blast hits to 862 proteins in 155 species including archaea, bacteria, metazoa, fungi, plants and viruses This protein belongs to the TLS1 family, is associated with the spliceosome, and is overexpressed in multiple cancer cell lines in humans [11]. Hepatocellular carcinoma-associated antigen 587 (HCA587) has been found to be the protein most similar to HCA59, and its peptides could bind to DCs [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
