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

Chris J.C. Johnston, Danielle J. Smyth, Ravindra B. Kodali, Madeleine P.J. White, Yvonne Harcus, Kara J. Filbey, James P. Hewitson, Cynthia S. Hinck, Alasdair Ivens, Andrea M. Kemter, Anna O. Kildemoes, Thierry Le Bihan, Dinesh C. Soares, Stephen M. Anderton, Thomas Brenn, Stephen J. Wigmore, Hannah V. Woodcock, Rachel C. Chambers, Andrew P. Hinck, Henry J. McSorleyRick M. Maizels

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish (US)
Article number1741
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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