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. McSorley; Rick M. Maizels

doi:10.1038/s41467-017-01886-6

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 (Lead / Corresponding author)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

129 Citations (Scopus)

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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 language	English
Article number	1741
Pages (from-to)	1-13
Number of pages	13
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/s41467-017-01886-6
Publication status	Published - 23 Nov 2017

Keywords

Immune evasion
Parasitic infection
Regulatory T cells
Transforming growth factor beta

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-017-01886-6Licence: CC BY

Final Published VersionFinal published version, 2.11 MBLicence: CC BY

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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., ... Maizels, R. M. (2017). A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications, 8, 1-13. Article 1741. https://doi.org/10.1038/s41467-017-01886-6

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

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.",

keywords = "Immune evasion, Parasitic infection, Regulatory T cells, Transforming growth factor beta",

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

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Johnston, CJC, Smyth, DJ, Kodali, RB, White, MPJ, Harcus, Y, Filbey, KJ, Hewitson, JP, Hinck, CS, Ivens, A, Kemter, AM, Kildemoes, AO, Le Bihan, T, Soares, DC, Anderton, SM, Brenn, T, Wigmore, SJ, Woodcock, HV, Chambers, RC, Hinck, AP, McSorley, HJ & Maizels, RM 2017, 'A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells', Nature Communications, vol. 8, 1741, pp. 1-13. https://doi.org/10.1038/s41467-017-01886-6

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AU - Johnston, Chris J. C.

AU - Smyth, Danielle J.

AU - Kodali, Ravindra B.

AU - White, Madeleine P. J.

AU - Harcus, Yvonne

AU - Filbey, Kara J.

AU - Hewitson, James P.

AU - Hinck, Cynthia S.

AU - Ivens, Alasdair

AU - Kemter, Andrea M.

AU - Kildemoes, Anna O.

AU - Le Bihan, Thierry

AU - Soares, Dinesh C.

AU - Anderton, Stephen M.

AU - Brenn, Thomas

AU - Wigmore, Stephen J.

AU - Woodcock, Hannah V.

AU - Chambers, Rachel C.

AU - Hinck, Andrew P.

AU - McSorley, Henry J.

AU - Maizels, Rick M.

PY - 2017/11/23

Y1 - 2017/11/23

N2 - 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.

AB - 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.

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KW - Parasitic infection

KW - Regulatory T cells

KW - Transforming growth factor beta

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M3 - Article

C2 - 29170498

AN - SCOPUS:85035047533

SN - 2041-1723

VL - 8

SP - 1

EP - 13

JO - Nature Communications

JF - Nature Communications

M1 - 1741

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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McSorley, Henry

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

Abstract

Keywords

ASJC Scopus subject areas

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McSorley, Henry

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