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

Research output: Contribution to journalArticle

  • Authors:
  • CJC Johnston
  • DJ Smyth
  • RB Kodali
  • MPJ White
  • Y Harcus
  • And 9 others
  • External authors:
  • KJ Filbey
  • JP Hewitson
  • CS Hinck
  • A Ivens
  • AM Kemter
  • AO Kildemoes
  • Bihan T Le
  • DC Soares
  • RM Maizels

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.

Bibliographical metadata

Original languageEnglish
JournalNature Communications
DOIs
Publication statusPublished - 23 Nov 2017