- Megan Osbourn
- Francesco Vacca
- E. Suzanne Cohen
- Ian C. Scott
- Matilda Toivakka
- Andrea M. Kemter
- Dennis Hoving
- Holly Henderson
- Andrea Gonzàlez-cìscar
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Rights statement: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 2.97 MB, PDF document
Licence: CC BY
Original language | English |
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Pages (from-to) | 739-751.e5 |
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Number of pages | 18 |
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Journal | Immunity |
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Volume | 47 |
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Issue number | 4 |
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DOIs | |
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Publication status | Published - 17 Oct 2017 |
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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.
ID: 46311973