A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells

Johnston, C. J.C. et al. (2017) A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications, 8, 1741. (doi: 10.1038/s41467-017-01886-6) (PMID:29170498) (PMCID:PMC5701006)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: White, Dr Madeleine and Kemter, Miss Andrea and Smyth, Dr Danielle and Maizels, Professor Rick
• Authors: Johnston, C. J.C., Smyth, D. J., Kodali, R. B., White, M. P.J., Harcus, Y., Filbey, K. J., Hewitson, J. P., Hinck, C. S., Ivens, A., Kemter, A. M., Kildemoes, A. O., Le Bihan, T., Soares, D. C., Anderton, S. M., Brenn, T., Wigmore, S. J., Woodcock, H. V., Chambers, R. C., Hinck, A. P., McSorley, H. J., and Maizels, R. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Nature Communications 8: 1741
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
76522	1	Helminths and the Immune System: Regulation, Regulators and Immunity	Richard Maizels	Wellcome Trust (WELLCOTR)	106122/A/14/Z	III - PARASITOLOGY
37179	9	The Wellcome Centre for Molecular Parasitology ( Core Support )	Andrew Waters	Wellcome Trust (WELLCOTR)	104111/Z/14/Z & A	III - PARASITOLOGY