HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33

作者：O**ourn Megan; Soares Dinesh C; Vacca Francesco; Cohen E Suzanne; Scott Ian C; Gregory William F; Smyth Danielle J; Toivakka Matilda; Kemter Andrea M; Le Bihan Thierry; Wear Martin; Hoving Dennis; Filbey Kara J; Hewitson James P; Henderson Holly; Gonzalez Ciscar Andrea; Errington Claire; Vermeren Sonja; Astier Anne L; Wallace William A; Schwarze Jurgen; Ivens Alasdair C; Maizels Rick M; McSorley Henry J

来源：Immunity, 2017, 47(4): 739-+.

DOI：10.1016/j.immuni.2017.09.015

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 Alar-min 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.

• 出版日期2017-10-17