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Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti

Author

Listed:
  • Yoann Saucereau

    (University of Cambridge)

  • Thomas H. Wilson

    (University of Cambridge)

  • Matthew C. K. Tang

    (University of Cambridge)

  • Martin C. Moncrieffe

    (University of Cambridge)

  • Steven W. Hardwick

    (University of Cambridge)

  • Dimitri Y. Chirgadze

    (University of Cambridge)

  • Sandro G. Soares

    (University of Cambridge)

  • Maria Jose Marcaida

    (Ecole Polytechnique Fédérale de Lausanne)

  • Nicholas J. Gay

    (University of Cambridge)

  • Monique Gangloff

    (University of Cambridge)

Abstract

Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response.

Suggested Citation

  • Yoann Saucereau & Thomas H. Wilson & Matthew C. K. Tang & Martin C. Moncrieffe & Steven W. Hardwick & Dimitri Y. Chirgadze & Sandro G. Soares & Maria Jose Marcaida & Nicholas J. Gay & Monique Gangloff, 2022. "Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32690-6
    DOI: 10.1038/s41467-022-32690-6
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    References listed on IDEAS

    as
    1. Nikolaj Kulahin Roed & Cristina M. Viola & Ole Kristensen & Gerd Schluckebier & Mathias Norrman & Waseem Sajid & John D. Wade & Asser Sloth Andersen & Claus Kristensen & Timothy R. Ganderton & Johan P, 2018. "Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Sarah E. Ewald & Bettina L. Lee & Laura Lau & Katherine E. Wickliffe & Guo-Ping Shi & Harold A. Chapman & Gregory M. Barton, 2008. "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor," Nature, Nature, vol. 456(7222), pages 658-662, December.
    3. Jules A. Hoffmann, 2003. "The immune response of Drosophila," Nature, Nature, vol. 426(6962), pages 33-38, November.
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