| First Author | Osbourn M | Year | 2017 |
| Journal | Immunity | Volume | 47 |
| Issue | 4 | Pages | 739-751.e5 |
| PubMed ID | 29045903 | Mgi Jnum | J:274274 |
| Mgi Id | MGI:6141045 | Doi | 10.1016/j.immuni.2017.09.015 |
| Citation | Osbourn M, et al. (2017) HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33. Immunity 47(4):739-751.e5 |
| abstractText | 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. |
