Abstract

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.

Details

Title
A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells
Author
Johnston, Chris J C 1 ; Smyth, Danielle J 2 ; Kodali, Ravindra B 3 ; White, Madeleine P J 4 ; Harcus, Yvonne 5 ; Filbey, Kara J 6 ; Hewitson, James P 7   VIAFID ORCID Logo  ; Hinck, Cynthia S 3 ; Ivens, Alasdair 5 ; Kemter, Andrea M 5 ; Kildemoes, Anna O 8   VIAFID ORCID Logo  ; Thierry Le Bihan 5 ; Soares, Dinesh C 9   VIAFID ORCID Logo  ; Anderton, Stephen M 9 ; Brenn, Thomas 10   VIAFID ORCID Logo  ; Wigmore, Stephen J 11 ; Woodcock, Hannah V 12 ; Chambers, Rachel C 12 ; Hinck, Andrew P 3 ; McSorley, Henry J 13 ; Maizels, Rick M 4 

1  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK 
2  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK 
3  Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 
4  Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK 
5  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK 
6  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; Malaghan Institute of Medical Research, Wellington, New Zealand 
7  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; Department of Biology, University of York, York, UK 
8  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; Section for Parasitology and Aquatic Diseases, Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark 
9  MRC Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK 
10  Department of Pathology, Western General Hospital, University of Edinburgh, Edinburgh, UK 
11  Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK 
12  Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Institute, University College London, London, UK 
13  Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; MRC Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK 
Pages
1-13
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-01886-6
ProQuest document ID
1967846662
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.