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Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor

Author

Listed:
  • Olivia J. S. Macleod

    (University of Cambridge)

  • Alexander D. Cook

    (University of Oxford
    University of Oxford)

  • Helena Webb

    (University of Cambridge)

  • Mandy Crow

    (University of Cambridge)

  • Roisin Burns

    (University of Cambridge)

  • Maria Redpath

    (University of Cambridge)

  • Stefanie Seisenberger

    (University of Cambridge)

  • Camilla E. Trevor

    (University of Cambridge)

  • Lori Peacock

    (University of Bristol)

  • Angela Schwede

    (University of Cambridge)

  • Nicola Kimblin

    (University of Cambridge)

  • Amanda F. Francisco

    (London School of Hygiene and Tropical Medicine)

  • Julia Pepperl

    (University of Cambridge)

  • Steve Rust

    (Biopharmaceuticals R&D, AstraZeneca)

  • Paul Voorheis

    (Trinity College Dublin)

  • Wendy Gibson

    (University of Bristol)

  • Martin C. Taylor

    (London School of Hygiene and Tropical Medicine)

  • Matthew K. Higgins

    (University of Oxford
    University of Oxford)

  • Mark Carrington

    (University of Cambridge)

Abstract

African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.

Suggested Citation

  • Olivia J. S. Macleod & Alexander D. Cook & Helena Webb & Mandy Crow & Roisin Burns & Maria Redpath & Stefanie Seisenberger & Camilla E. Trevor & Lori Peacock & Angela Schwede & Nicola Kimblin & Amanda, 2022. "Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32728-9
    DOI: 10.1038/s41467-022-32728-9
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    References listed on IDEAS

    as
    1. Anaïs Menny & Marina Serna & Courtney M. Boyd & Scott Gardner & Agnel Praveen Joseph & B. Paul Morgan & Maya Topf & Nicholas J. Brooks & Doryen Bubeck, 2018. "CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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