Johnston, Chris J. C., Smyth, Danielle J., Kodali, Ravindra B. et al. (18 more authors) (2017) A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications. 1741. ISSN 2041-1723
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2017 |
Keywords: | Amino Acid Sequence, Animals, Antigens, Helminth/chemistry, Female, Helminth Proteins/chemistry, Host-Pathogen Interactions/genetics, Humans, Immune Evasion/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Molecular Mimicry/genetics, Nematospiroides dubius/genetics, Protein Binding, Protein Domains, Receptors, Transforming Growth Factor beta/metabolism, Strongylida Infections/immunology, T-Lymphocytes, Regulatory/immunology, Transforming Growth Factor beta/metabolism |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 27 Nov 2017 10:10 |
Last Modified: | 21 Mar 2024 00:15 |
Published Version: | https://doi.org/10.1038/s41467-017-01886-6 |
Status: | Published |
Refereed: | Yes |
Identification Number: | https://doi.org/10.1038/s41467-017-01886-6 |
Related URLs: |