Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection
Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection
复制标题
布鲁氏菌 TIR 样蛋白 TcpB/Btp1 特异性靶向宿主接头蛋白 MAL/TIRAP 促进感染
DOI：
10.1016/j.bbrc.2016.06.064
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发表时间：
2016-08-26
影响因子：
3.1
通讯作者：
Li, Juan
中科院分区：
文献类型：
--
作者：
Li, Wenna;Ke, Yuehua;Li, Juan
已知布鲁氏菌可避免宿主免疫识别并削弱对感染的免疫反应。布鲁氏菌通过采用两种聪明的策略来实现这一点，这两种策略被称为隐形策略和劫持策略。布鲁氏菌的TIR结构域蛋白（TcpB/Btp1）被认为通过与toll样受体下游的接头结合，参与抑制宿主NF-kappa B的激活。然而，在哺乳动物中保存的5个含TIR结构域的适配器中，无论是MyD88还是MAL，甚至其他3个适配器，都没有被TcpB特异性靶向。本研究证实了TcpB对melitensis毒力的影响，并发现TcpB选择性靶向MAL，通过siRNA靶向MAL，我们发现来自B.melitensis的TcpB参与细胞内存活，MAL影响B.melitensis的细胞内复制。我们的研究结果证实，TcpB特异性靶向MAL/TIRAP，破坏下游信号通路，促进布鲁氏菌的宿主内存活。(C) 2016 Elsevier Inc.。版权所有。
Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-kappa B activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified. Here, we confirmed the effect of TcpB on B.melitensis virulence in mice and found that TcpB selectively targets MAL. By using siRNA against MAL, we found that TcpB from B.melitensis is involved in intracellular survival and that MAL affects intracellular replication of B.melitensis. Our results confirm that TcpB specifically targets MAL/TIRAP to disrupt downstream signaling pathways and promote intra-host survival of Brucella spp. (C) 2016 Elsevier Inc. All rights reserved.