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      Hepatocellular carcinoma-associated antigen 59 of Haemonchus contortus modulates the functions of PBMCs and the differentiation and maturation of monocyte-derived dendritic cells of goats in vitro

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          Abstract

          Background

          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. However, its immunomodulatory effects on host cells are poorly understood.

          Methods

          Here, 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.

          Results

          The 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.

          Conclusions

          Our 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.

          Electronic supplementary material

          The online version of this article (10.1186/s13071-019-3375-1) contains supplementary material, which is available to authorized users.

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          Most cited references54

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          Nitric oxide in immunity and inflammation.

          John Coleman (2001)
          Nitric oxide (NO) is synthesised by many cell types involved in immunity and inflammation. The principal enzyme involved is the inducible type-2 isoform of nitric oxide synthase (NOS-2), which produces high-level sustained NO synthesis. NO is important as a toxic defense molecule against infectious organisms. It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and natural killer cells. However, the role of NO in nonspecific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. NO does not act through a receptor-its target cell specificity depends on its concentration, its chemical reactivity, the vicinity of target cells and the way that target cells are programmed to respond. At high concentrations as generated by NOS-2, NO is rapidly oxidised to reactive nitrogen oxide species (RNOS) that mediate most of the immunological effects of NOS-2-derived NO. RNOS can S-nitrosate thiols to modify key signalling molecules such as kinases and transcription factors. Several key enzymes in mitochondrial respiration are also inhibited by RNOS and this leads to a depletion of ATP and cellular energy. A combination of these interactions may explain the multiple actions of NO in the regulation of immune and inflammatory cells.
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            The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery

            Roz Laing, Taisei Kikuchi, Axel Martinelli … (2013)
            Background The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans. Results Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates. Conclusions The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites.
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              Leishmania and the macrophage: a multifaceted interaction.

              Maria Podinovskaia, Albert Descoteaux (2015)
              Leishmania, the causative agent of leishmaniases, is an intracellular parasite of macrophages, transmitted to humans via the bite of its sand fly vector. This protozoan organism has evolved strategies for efficient uptake into macrophages and is able to regulate phagosome maturation in order to make the phagosome more hospitable for parasite growth and to avoid destruction. As a result, macrophage defenses such as oxidative damage, antigen presentation, immune activation and apoptosis are compromised whereas nutrient availability is improved. Many Leishmania survival factors are involved in shaping the phagosome and reprogramming the macrophage to promote infection. This review details the complexity of the host-parasite interactions and summarizes our latest understanding of key events that make Leishmania such a successful intracellular parasite.
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                Author and article information

                Contributors
                QiangQiang Wang: 2016107053@naju.edu.cn
                LingYan Wu: wuly@nju-nbri.com
                Muhammad Waqqas Hasan: 2015207037@njau.edu.cn
                MingMin Lu: 2015207018@njau.edu.cn
                WenJuan Wang: 2015107058@njau.edu.cn
                RuoFeng Yan: yanruofeng@njau.edu.cn
                LiXin Xu: xulixin@njau.edu.cn
                XiaoKai Song: songxiaokai@njau.edu.cn
                XiangRui Li: lixiangrui@njau.edu.cn
                Journal
                Journal ID (nlm-ta): Parasit Vectors
                Journal ID (iso-abbrev): Parasit Vectors
                Title: Parasites & Vectors
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-3305
                Publication date (Electronic): 14 March 2019
                Publication date PMC-release: 14 March 2019
                Publication date Collection: 2019
                Volume: 12
                Electronic Location Identifier: 105
                Affiliations
                ISNI 0000 0000 9750 7019, GRID grid.27871.3b, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, , Nanjing Agricultural University, ; Nanjing, Jiangsu PR China
                Article
                Publisher ID: 3375
                DOI: 10.1186/s13071-019-3375-1
                PMC ID: 6416944
                PubMed ID: 30871600
                SO-VID: 117135f8-de1f-4bf6-89c3-730b2416372a
                Copyright © © The Author(s) 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 24 October 2018
                Date accepted : 5 March 2019
                Funding
                Funded by: The National Key Research and Development Program of China
                Award ID: 2017YFD0501200
                Award Recipient :
                Funded by: the National Key Basic Research Program (973 Program) of P.R. China
                Award ID: 2015CB150300
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Parasitology
                Keywords: hca59,haemonchus contortus,dendritic cells,pbmcs,immunomodulatory effects
                Data availability:
                ScienceOpen disciplines: Parasitology
                Keywords: hca59, haemonchus contortus, dendritic cells, pbmcs, immunomodulatory effects

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