A helminth-derived suppressor of ST2 blocks allergic responses

Vacca, F. et al. (2020) A helminth-derived suppressor of ST2 blocks allergic responses. eLife, 9, e54017. (doi: 10.7554/elife.54017) (PMID:32420871) (PMCID:PMC7234810)

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 IL-33-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.

• Item Type: Articles
• Additional Information: This was work was funded by awards to HJM from LONGFONDS | Accelerate as part of the AWWA project, and the Medical Research Council (MR/S000593/1).
• Keywords: Research Article, Immunology and Inflammation, Microbiology and Infectious Disease, allergy, asthma, Helminth, parasite, IL-33, ST2, Human, Mouse.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Heieis, Graham Anthony and Webster, Miss Holly and Perona-Wright, Dr Georgia

Creator Roles

Heieis, G.: Investigation, Methodology, Writing – review and editing
Webster, H.: Investigation, Methodology, Writing – review and editing
Perona-Wright, G.: Conceptualization, Supervision, Investigation, Methodology, Writing – review and editing

• Authors: Vacca, F., Chauché, C., Jamwal, A., Hinchy, E. C., Heieis, G., Webster, H., Ogunkanbi, A., Sekne, Z., Gregory, W. F., Wear, M., Perona-Wright, G., Higgins, M. K., Nys, J. A., Cohen, E. S., and McSorley, H. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: eLife
• Publisher: eLife Sciences Publications
• ISSN: 2050-084X
• ISSN (Online): 2050-084X
• Copyright Holders: Copyright © 2020 Vacca et al
• First Published: First published in eLife 9: e54017
• Publisher Policy: Reproduced under a creative commons licence