Details

Autor(en) / Beteiligte

• Osbourn, 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
• Gonzàlez-Cìscar, Andrea
• Errington, Claire
• Vermeren, Sonja
• Astier, Anne L.
• Wallace, William A.
• Schwarze, Jürgen
• Ivens, Alasdair C.
• Maizels, Rick M.
• McSorley, Henry J.

Titel

HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33

Ist Teil von

• Immunity (Cambridge, Mass.), 2017-10, Vol.47 (4), p.739-751.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •HpARI is a suppressor of IL-33 release and consequent allergic sensitization•HpARI binds active IL-33 and nuclear DNA, tethering IL-33 within necrotic cells•HpARI is active against both human and murine IL-33 Osbourn et al identified HpARI, a protein secreted by a helminth parasite that is capable of suppressing allergic responses. HpARI binds to IL-33 (a critical inducer of allergy) and nuclear DNA, preventing the release of IL-33 from necrotic epithelial cells.