A helminth-derived suppressor of ST2 blocks allergic responses

Francesco Vacca, Caroline Chauché, Abhishek Jamwal, Elizabeth C. Hinchy, Graham Heieis, Holly Webster, Adefunke Ogunkanbi, Zala Sekne, William F. Gregory, Martin A. Wear, Georgia Perona-Wright, Matthew K Higgins, Josquin Nys, E. Suzanne Cohen, Henry McSorley (Lead / Corresponding author)

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Abstract

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.
Original languageEnglish
Article numbere54017
Pages (from-to)1-20
Number of pages20
JournaleLife
Volume9
DOIs
Publication statusPublished - 18 May 2020

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Vacca, F., Chauché, C., Jamwal, A., Hinchy, E. C., Heieis, G., Webster, H., Ogunkanbi, A., Sekne, Z., Gregory, W. F., Wear, M. A., Perona-Wright, G., Higgins, M. K., Nys, J., Cohen, E. S., & McSorley, H. (2020). A helminth-derived suppressor of ST2 blocks allergic responses. eLife, 9, 1-20. [e54017]. https://doi.org/10.7554/eLife.54017