HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.
HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.
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DOI：
10.1016/j.immuni.2017.09.015
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发表时间：
2017-10-17
期刊：
影响因子：
32.4
通讯作者：
McSorley HJ
中科院分区：
文献类型：
--
作者：
Osbourn M;Soares DC;Vacca F;Cohen ES;Scott IC;Gregory WF;Smyth DJ;Toivakka M;Kemter AM;le Bihan T;Wear M;Hoving D;Filbey KJ;Hewitson JP;Henderson H;Gonzàlez-Cìscar A;Errington C;Vermeren S;Astier AL;Wallace WA;Schwarze J;Ivens AC;Maizels RM;McSorley HJ
蠕虫寄生虫感染与过敏反应性的改善有关，但缺乏对这种联系的机制的见解。小鼠寄生虫Heligmosomoides polygyrus分泌的产物通过干扰白细胞介素-33（IL-33）途径抑制2型（过敏性）免疫应答。在这里，我们确定了多脑回血吸虫Alarmin释放抑制剂（HpARI），一种IL-33抑制性26-kDa蛋白，含有三个预测的补体控制蛋白（CCP）模块。在体内，重组HpARI废除IL-33，第2组先天淋巴细胞（ILC2）和嗜酸性粒细胞的反应链格孢变应原管理，并减少嗜酸性粒细胞的反应，巴西日本圆线虫，增加寄生虫的负担。HpARI直接与小鼠和人IL-33（在细胞因子的活化状态下）结合，并且还通过其N-末端CCP模块对（CCP 1/2）与核DNA结合，将活性IL-33束缚在坏死细胞内，防止其释放，并阻止2型过敏反应的启动。因此，HpARI采用一种新的分子策略来抑制感染和过敏中的2型免疫。HpARI是IL-33释放和随后的过敏性致敏的抑制剂HpARI结合活性IL-33和核DNA，将IL-33束缚在坏死细胞内HpARI对人和鼠IL-33都有活性Osbourn等鉴定了HpARI，一种由蠕虫寄生虫分泌的能够抑制过敏反应的蛋白质。HpARI与IL-33（过敏的关键诱导物）和核DNA结合，阻止IL-33从坏死上皮细胞释放。
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. 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.
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影响因子：
14.9
作者：
Howe KL;Bolt BJ;Cain S;Chan J;Chen WJ;Davis P;Done J;Down T;Gao S;Grove C;Harris TW;Kishore R;Lee R;Lomax J;Li Y;Muller HM;Nakamura C;Nuin P;Paulini M;Raciti D;Schindelman G;Stanley E;Tuli MA;Van Auken K;Wang D;Wang X;Williams G;Wright A;Yook K;Berriman M;Kersey P;Schedl T;Stein L;Sternberg PW
通讯作者：
Sternberg PW
DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
影响因子：
2.1
作者：
Lawrence, RA;Gray, CA;Maizels, RM
通讯作者：
Maizels, RM
影响因子：
6.7
作者：
Hewitson, James P.;Ivens, Al C.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.
影响因子：
30.8
作者：
Bonnelykke, Klaus;Sleiman, Patrick;Bisgaard, Hans
通讯作者：
Bisgaard, Hans