Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy

McSorley, H.J., Blair, N.F., Smith, K.A., McKenzie, A.N.J. and Maizels, R.M. (2014) Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunology, 7(5), pp. 1068-1078. (doi: 10.1038/mi.2013.123) (PMID:24496315) (PMCID:PMC4016792)

[img]
Preview
Text
205010.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

936kB

Abstract

Helminth parasites such as the nematode Heligmosomoides polygyrus strongly inhibit T helper type 2 (Th2) allergy, as well as colitis and autoimmunity. Here, we show that the soluble excretory/secretory products of H. polygyrus (HES) potently suppress inflammation induced by allergens from the common fungus Alternaria alternata. Alternaria extract, when administered to mice intranasally with ovalbumin (OVA) protein, induces a rapid (1–48 h) innate response while also priming an OVA-specific Th2 response that can be evoked 14 days later by intranasal administration of OVA alone. In this model, HES coadministration with Alternaria/OVA suppressed early IL-33 release, innate lymphoid cell (ILC) production of IL-4, IL-5, and IL-13, and localized eosinophilia. Upon OVA challenge, type 2 ILC (ILC2)/Th2 cytokine production and eosinophilia were diminished in HES-treated mice. HES administration 6 h before Alternaria blocked the allergic response, and its suppressive activity was abolished by heat treatment. Administration of recombinant IL-33 at sensitization with Alternaria/OVA/HES abrogated HES suppression of OVA-specific responses at challenge, indicating that suppression of early Alternaria-induced IL-33 release could be central to the anti-allergic effects of HES. Thus, this helminth parasite targets IL-33 production as part of its armory of suppressive effects, forestalling the development of the type 2 immune response to infection and allergic sensitization.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maizels, Professor Rick
Authors: McSorley, H.J., Blair, N.F., Smith, K.A., McKenzie, A.N.J., and Maizels, R.M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Mucosal Immunology
Publisher:Springer Nature
ISSN:1933-0219
ISSN (Online):1935-3456
Published Online:05 February 2014
Copyright Holders:Copyright © 2014 Society for Mucosal Immunology
First Published:First published in Mucosal Immunology 7(5):1068-1078
Publisher Policy:Reproduced under a Creative Commons license

University Staff: Request a correction | Enlighten Editors: Update this record