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

• DOI: 10.1038/s41467-017-01886-6
• Publication Date: 2017-11-17T21:15:10Z
• Authors: Chris J. C. Johnston; Danielle J. Smyth; Ravindra B. Kodali; Madeleine P. J. W...; 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. McSorley; Rick M. Maizels
• Keywords: Parasitic infection; 570; 1300; Science; 1600; 610; Mice, Transgenic; T-Lymphocytes, Regulatory; regulatory T cells; 3100; Article; Mice; 03 medical and health sciences; 0302 clinical medicine; Protein Domains; Transforming Growth Factor beta; name=General Biochemistry,Genetics and Molecular Biology; Animals; Humans; Amino Acid Sequence; immune evasion; Immune Evasion; Strongylida Infections; transforming growth factor beta; Mice, Inbred BALB C; Nematospiroides dubius; /dk/atira/pure/subjectarea/asjc/1300/1300; Immune evasion; Q; Molecular Mimicry; Regulatory T cells; Helminth Proteins; 3. Good health; Mice, Inbred C57BL; parasitic infection; name=General Physics and Astronomy; Antigens, Helminth; Host-Pathogen Interactions; Transforming growth factor beta; Female; /dk/atira/pure/subjectarea/asjc/3100/3100; name=General Chemistry; Receptors, Transforming Growth Factor beta; /dk/atira/pure/subjectarea/asjc/1600/1600; Protein Binding

AbstractHelminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasiteHeligmosomoides polygyruscan 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 anH. polygyrusTGF-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.