Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion
Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion
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肠出血性大肠杆菌 Tir 抑制 TAK1 激活并介导免疫逃避
DOI：
10.1080/22221751.2019.1620589
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发表时间：
2019-01
影响因子：
13.2
通讯作者：
Yan Dapeng
中科院分区：
文献类型：
--
作者：
Zhou Ruixue;Chen Zijuan;Hao Doudou;Wang Yu;Zhang Yihua;Yi Xianfu;Lyu Liang Dong;Liu Haipeng;Zou Quanming;Chu Yiwei;Ge Baoxue;Yan Dapeng
许多病原体通过各种免疫逃避策略感染宿主。然而，病原体蛋白调节和逃避宿主免疫应答的分子机制仍不清楚。肠出血性大肠杆菌（Enterohemorrhagic Escherichia coli，EHEC）是一种可诱导丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAP）（Erk、Jnk和p38 MAPK）和NF-κB B通路活化并产生促炎性细胞因子的致病菌，可引起出血性结肠炎和溶血性尿毒综合征等肠道疾病。转化生长因子β激活激酶-1（TAK 1）是参与不同先天免疫信号传导途径的关键调节因子。在这里，我们报告说，肠出血性大肠杆菌易位的内膜受体（Tir）蛋白抑制肠出血性大肠杆菌诱导的促炎细胞因子的表达，通过与宿主酪氨酸磷酸酶SHP-1，这是依赖于磷酸化的免疫受体酪氨酸为基础的抑制基序（ITIM）。从机制上讲，EHEC Tir与SHP-1的结合促进了SHP-1向TAK 1的募集，并抑制了TAK 1的磷酸化，然后负调控了TAK 1的K63连接的多聚泛素化和下游信号转导。总之，这些结果表明，EHEC Tir通过抑制TAK 1的活化来负调节促炎反应，TAK 1对于免疫逃避是必需的，并且可能是治疗细菌感染的潜在靶标。
ABSTRACT Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor β-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection.
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影响因子：
24.1
作者：
X. Zhuang;Zijuan Chen;Chenxi He;Lin Wang;Ruixue Zhou;Dapeng Yan;Baoxue Ge
通讯作者：
X. Zhuang;Zijuan Chen;Chenxi He;Lin Wang;Ruixue Zhou;Dapeng Yan;Baoxue Ge
影响因子：
30.5
作者：
Hamerman, JA;Tchao, NK;Lanier, LL
通讯作者：
Lanier, LL
TAB1 的 O-GlcNAc 酰化调节 TAK1 介导的细胞因子释放。
影响因子：
11.4
作者：
Pathak, Shalini;Borodkin, Vladimir S.;Albarbarawi, Osama;Campbell, David G.;Ibrahim, Adel;van Aalten, Daan M. F.
通讯作者：
van Aalten, Daan M. F.
影响因子：
3.6
作者：
Chen, Wen-Pin;Tzeng, Hsiao-Jung;Su, Ming-Jai
通讯作者：
Su, Ming-Jai
影响因子：
5.5
作者：
Jongdae Lee;Laurence Mira‐Arbibe;R. Ulevitch
通讯作者：
Jongdae Lee;Laurence Mira‐Arbibe;R. Ulevitch