The pervasive effects of recombinant  Fasciola gigantica  Ras-related protein Rab10 on the functions of goat peripheral blood mononuclear cells

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Abstract

Background

Fasciola gigantica-induced immunomodulation is a major hurdle faced by the host for controlling infection. Here, we elucidated the role of F. gigantica Ras-related protein Rab10 (FgRab10) in the modulation of key functions of peripheral blood mononuclear cells (PBMCs) of goats.

Methods

We cloned and expressed recombinant FgRab10 (rFgRab10) protein and examined its effects on several functions of goat PBMCs. Protein interactors of rFgRab10 were predicted in silico by querying the databases Intact, String, BioPlex and BioGrid. In addition, a total energy analysis of each of the identified interactions was also conducted. Gene Ontology (GO) enrichment analysis was carried out using FuncAssociate 3.0.

Results

The FgRab10 gene (618 bp), encodes 205-amino-acid residues with a molecular mass of ~23 kDa, had complete nucleotide sequence homology with F. hepatica Ras family protein gene (PIS87503.1). The rFgRab10 protein specifically cross-reacted with anti- Fasciola antibodies as shown by Western blot and immunofluorescence analysis. This protein exhibited multiple effects on goat PBMCs, including increased production of cytokines [interleukin-2 (IL-2), IL-4, IL-10, transforming growth factor beta (TGF-β) and interferon gamma (IFN-γ)] and total nitric oxide (NO), enhancing apoptosis and migration of PBMCs, and promoting the phagocytic ability of monocytes. However, it significantly inhibited cell proliferation. Homology modelling revealed 63% identity between rFgRab10 and human Rab10 protein (Uniprot ID: P61026). Protein interaction network analysis revealed more stabilizing interactions between Rab proteins geranylgeranyltransferase component A 1 (CHM) and Rab proteins geranylgeranyltransferase component A 2 (CHML) and rFgRab10 protein. Gene Ontology analysis identified RabGTPase mediated signaling as the most represented pathway.

Conclusions

rFgRab10 protein exerts profound influences on various functions of goat PBMCs. This finding may help explain why F. gigantica is capable of provoking recognition by host immune cells, less capable of destroying this successful parasite.

Electronic supplementary material

The online version of this article (10.1186/s13071-018-3148-2) contains supplementary material, which is available to authorized users.

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Most cited references 37

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ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules.

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The BioGRID interaction database: 2017 update

Andrew Chatr-aryamontri, Rose Oughtred, Lorrie Boucher … (2016)

The Biological General Repository for Interaction Datasets (BioGRID: https://thebiogrid.org) is an open access database dedicated to the annotation and archival of protein, genetic and chemical interactions for all major model organism species and humans. As of September 2016 (build 3.4.140), the BioGRID contains 1 072 173 genetic and protein interactions, and 38 559 post-translational modifications, as manually annotated from 48 114 publications. This dataset represents interaction records for 66 model organisms and represents a 30% increase compared to the previous 2015 BioGRID update. BioGRID curates the biomedical literature for major model organism species, including humans, with a recent emphasis on central biological processes and specific human diseases. To facilitate network-based approaches to drug discovery, BioGRID now incorporates 27 501 chemical–protein interactions for human drug targets, as drawn from the DrugBank database. A new dynamic interaction network viewer allows the easy navigation and filtering of all genetic and protein interaction data, as well as for bioactive compounds and their established targets. BioGRID data are directly downloadable without restriction in a variety of standardized formats and are freely distributed through partner model organism databases and meta-databases.

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Author and article information

Contributors

Ai-Ling Tian: ailingtian@hotmail.com

MingMin Lu: 2015207018@njau.edu.cn

Fu-Kai Zhang: zhangfukai0519@outlook.com

Guillermo Calderón-Mantilla: calderon@ebi.ac.uk

Evangelia Petsalaki: petsalaki@ebi.ac.uk

XiaoWei Tian: 2017207011@njau.edu.cn

WenJuan Wang: 2015107058@njau.edu.cn

Si-Yang Huang: siyang.huang@hotmail.com

XiangRui Li: lixiangrui@njau.edu.cn

Hany M. Elsheikha: hany.elsheikha@nottingham.ac.uk

Xing-Quan Zhu: xingquanzhu1@hotmail.com

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): 6 November 2018

Publication date PMC-release: 6 November 2018

Publication date Collection: 2018

Volume: 11

Electronic Location Identifier: 579

Affiliations

[1 ]ISNI 0000 0001 0526 1937, GRID grid.410727.7, State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, , Chinese Academy of Agricultural Sciences, ; Lanzhou, Gansu Province 730046 People’s Republic of China

[2 ]ISNI 0000 0000 9750 7019, GRID grid.27871.3b, College of Veterinary Medicine, , Nanjing Agricultural University, ; Nanjing, 210095 People’s Republic of China

[3 ]ISNI 0000 0000 9709 7726, GRID grid.225360.0, European Molecular Biology Laboratory-European Bioinformatics Institute, ; Wellcome Genome Campus, Hinxton, CB10 1SD UK

[4 ]GRID grid.268415.c, College of Veterinary Medicine, , Yangzhou University, ; Yangzhou, Jiangsu Province 225009 People’s Republic of China

[5 ]Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province 225009 People’s Republic of China

[6 ]ISNI 0000 0004 1936 8868, GRID grid.4563.4, Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, , University of Nottingham, ; Sutton Bonington Campus, Loughborough, LE12 5RD UK

Article

Publisher ID: 3148

DOI: 10.1186/s13071-018-3148-2

PMC ID: 6219056

PubMed ID: 30400957

SO-VID: 79294bb9-3d6f-464f-8412-4e07ca6f9404

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 : 15 June 2018

Date accepted : 14 October 2018

Funding

Funded by: the National Key Basic Research Program (973 Program) of China

Award ID: 2015CB150300

Award Recipient : Xing-Quan Zhu

Funded by: the Elite Program of Chinese Academy of Agricultural Sciences

Custom metadata

ScienceOpen disciplines: Parasitology

Keywords: fasciola gigantica,ras-related protein rab10,recombinant proteins,peripheral blood mononuclear cells,immunomodulation

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ScienceOpen disciplines: Parasitology

Keywords: fasciola gigantica, ras-related protein rab10, recombinant proteins, peripheral blood mononuclear cells, immunomodulation

The pervasive effects of recombinant Fasciola gigantica Ras-related protein Rab10 on the functions of goat peripheral blood mononuclear cells

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Abstract

Background

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Electronic supplementary material

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Malaria vaccine development

Most cited references 37

Nitric oxide and macrophage function.

ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules.

The BioGRID interaction database: 2017 update

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