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The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function

Author

Listed:
  • Allison J. Bancroft

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Colin W. Levy

    (University of Manchester)

  • Thomas A. Jowitt

    (Wellcome Trust Centre for Cell Matrix Research
    University of Manchester)

  • Kelly S. Hayes

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Seona Thompson

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Edward A. Mckenzie

    (University of Manchester)

  • Matthew D. Ball

    (University of Manchester)

  • Eamon Dubaissi

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Aidan P. France

    (University of Manchester)

  • Bruno Bellina

    (University of Manchester)

  • Catherine Sharpe

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Aleksandr Mironov

    (University of Manchester)

  • Sheila L. Brown

    (Lydia Becker Institute for Immunology and Inflammation
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester
    University of Manchester)

  • Peter C. Cook

    (Lydia Becker Institute for Immunology and Inflammation
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester
    University of Manchester)

  • Andrew MacDonald

    (Lydia Becker Institute for Immunology and Inflammation
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester
    University of Manchester)

  • David J. Thornton

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

  • Richard K. Grencis

    (Lydia Becker Institute for Immunology and Inflammation
    Wellcome Trust Centre for Cell Matrix Research
    Division of Infection, Immunity and Respiratory Medicine
    University of Manchester)

Abstract

Infection by soil transmitted parasitic helminths, such as Trichuris spp, are ubiquitous in humans and animals but the mechanisms determining persistence of chronic infections are poorly understood. Here we show that p43, the single most abundant protein in T. muris excretions/secretions, is non-immunogenic during infection and has an unusual sequence and structure containing subdomain homology to thrombospondin type 1 and interleukin (IL)−13 receptor (R) α2. Binding of p43 to IL-13, the key effector cytokine responsible for T. muris expulsion, inhibits IL-13 function both in vitro and in vivo. Tethering of p43 to matrix proteoglycans presents a bound source of p43 to facilitate interaction with IL-13, which may underpin chronic intestinal infection. Our results suggest that exploiting the biology of p43 may open up new approaches to modulating IL-13 function and control of Trichuris infections.

Suggested Citation

  • Allison J. Bancroft & Colin W. Levy & Thomas A. Jowitt & Kelly S. Hayes & Seona Thompson & Edward A. Mckenzie & Matthew D. Ball & Eamon Dubaissi & Aidan P. France & Bruno Bellina & Catherine Sharpe & , 2019. "The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09996-z
    DOI: 10.1038/s41467-019-09996-z
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    Cited by:

    1. Ömer F. Bay & Kelly S. Hayes & Jean-Marc Schwartz & Richard K. Grencis & Ian S. Roberts, 2023. "A genome-scale metabolic model of parasitic whipworm," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. María A. Duque-Correa & David Goulding & Faye H. Rodgers & J. Andrew Gillis & Claire Cormie & Kate A. Rawlinson & Allison J. Bancroft & Hayley M. Bennett & Magda E. Lotkowska & Adam J. Reid & Annelies, 2022. "Defining the early stages of intestinal colonisation by whipworms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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