HpARI protein secreted by a helminth parasite suppresses interleukin-33

Osbourn, M. et al. (2017) HpARI protein secreted by a helminth parasite suppresses interleukin-33. Immunity, 47(4), 739-751.e5. (doi: 10.1016/j.immuni.2017.09.015) (PMID:29045903) (PMCID:PMC5655542)

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Abstract

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine’s activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hoving, Mr Dennis and Smyth, Dr Danielle and Kemter, Miss Andrea and Maizels, Professor Rick
Authors: Osbourn, M., Soares, D. C., Vacca, F., Cohen, E. S., Scott, I. C., Gregory, W. F., Smyth, D. J., Toivakka, M., Kemter, A. M., le Bihan, T., Wear, M., Hoving, D., Filbey, K. J., Hewitson, J. P., Henderson, H., Gonzàlez-Cìscar, A., Errington, C., Vermeren, S., Astier, A. L., Wallace, W. A., Schwarze, J., Ivens, A. C., Maizels, R. M., and McSorley, H. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Elsevier
ISSN:1074-7613
ISSN (Online):1097-4180
Published Online:17 October 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Immunity 47(4): 739-751.e5
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
765221Helminths and the Immune System: Regulation, Regulators and ImmunityRichard MaizelsWellcome Trust (WELLCOTR)106122/A/14/ZIII - PARASITOLOGY
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY