An Immunosuppressive Tick Salivary Gland Protein DsCystatin Interferes With Toll-Like Receptor Signaling by Downregulating TRAF6.
An Immunosuppressive Tick Salivary Gland Protein DsCystatin Interferes With Toll-Like Receptor Signaling by Downregulating TRAF6.
复制标题
免疫抑制蜱唾液腺蛋白 DsCystatin 通过下调 TRAF6 干扰 Toll 样受体信号传导。
DOI：
10.3389/fimmu.2018.01245
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发表时间：
2018
影响因子：
7.3
通讯作者：
Dai J
中科院分区：
文献类型：
--
作者：
Sun T;Wang F;Pan W;Wu Q;Wang J;Dai J
蜱，吸血节肢动物，分泌免疫抑制分子，抑制宿主免疫反应，为病原体提供生存优势。在这项研究中，我们鉴定了一种新的蜱唾液蛋白——脱囊抑素的免疫抑制功能。解胱抑素直接与人组织蛋白酶L和B相互作用，抑制其酶活性。DsCystatin破坏了LPS或伯氏疏螺旋体刺激小鼠骨髓源性巨噬细胞（bmdm）的炎性细胞因子如il - 1β、IFNγ、TNFα和il - 6的表达。同样，DsCystatin通过下调CD80和CD86的表面表达抑制小鼠BMDMs和骨髓源性树突状细胞的激活。从机械上讲，DsCystatin抑制LPS或B. burgdorferi诱导的NFκB活化。我们首次发现dscystatin通过靶向TRAF6来减弱TLR4信号。DsCystatin增强lps诱导的自噬，通过自噬依赖的方式介导TRAF6降解，从而阻碍i - κ b α的下游磷酸化和nf - κ b的核转运。最后，DsCystatin减轻了伯氏疏螺旋体或完全弗氏佐剂诱导的小鼠关节炎模型的关节炎症。这些数据表明，脱syystatin是一种新型的免疫抑制蛋白，可用于炎症性疾病的治疗。
Ticks, blood-feeding arthropods, and secrete immunosuppressive molecules that inhibit host immune responses and provide survival advantages to pathogens. In this study, we characterized the immunosuppressive function of a novel tick salivary protein, DsCystatin, from Dermacentor silvarum of China. DsCystatin directly interacted with human Cathepsins L and B and inhibited their enzymatic activities. DsCystatin impaired the expression of inflammatory cytokines such as IL1β, IFNγ, TNFα, and IL6 from mouse bone marrow-derived macrophages (BMDMs) that had been stimulated with LPS or Borrelia burgdorferi. Consistently, DsCystatin inhibited the activation of mouse BMDMs and bone marrow-derived dendritic cells by downregulating the surface expression of CD80 and CD86. Mechanically, DsCystatin inhibited LPS- or B. burgdorferi-induced NFκB activation. For the first time, we identified that DsCystatin-attenuated TLR4 signaling by targeting TRAF6. DsCystatin enhanced LPS-induced autophagy, mediated TRAF6 degradation via an autophagy dependent manner, thereby impeded the downstream phosphorylation of IκBα and the nuclear transport of NFκB. Finally, DsCystatin relieved the joint inflammation in B. burgdorferi or complete Freund’s adjuvant induced mouse arthritis models. These data suggested that DsCystatin is a novel immunosuppressive protein and can potentially be used in the treatment of inflammatory diseases.
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影响因子：
3.1
作者：
Ma, Y;Seiler, KP;Weis, JJ
通讯作者：
Weis, JJ
影响因子：
3.2
作者：
Lieskovská J;Páleníková J;Langhansová H;Campos Chagas A;Calvo E;Kotsyfakis M;Kopecký J
通讯作者：
Kopecký J
影响因子：
3.3
作者：
Kotál J;Langhansová H;Lieskovská J;Andersen JF;Francischetti IM;Chavakis T;Kopecký J;Pedra JH;Kotsyfakis M;Chmelař J
通讯作者：
Chmelař J
DOI：
10.4049/jimmunol.1100529
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Horka H;Staudt V;Klein M;Taube C;Reuter S;Dehzad N;Andersen JF;Kopecky J;Schild H;Kotsyfakis M;Hoffmann M;Gerlitzki B;Stassen M;Bopp T;Schmitt E
通讯作者：
Schmitt E
影响因子：
4.8
作者：
Kotsyfakis, Michalis;Sa-Nunes, Anderson;Ribeiro, Jose M. C.
通讯作者：
Ribeiro, Jose M. C.