Inhibition of TLR4 signaling by Brucella TIR-containing protein TcpB-derived decoy peptides
Inhibition of TLR4 signaling by Brucella TIR-containing protein TcpB-derived decoy peptides
复制标题
含有布鲁氏菌 TIR 的蛋白 TcpB 衍生的诱饵肽对 TLR4 信号传导的抑制
DOI：
10.1016/j.ijmm.2016.05.003
复制
发表时间：
2016-09-01
影响因子：
4.1
通讯作者：
Chen, Zeliang
中科院分区：
文献类型：
--
作者：
Ke, Yuehua;Li, Wenna;Chen, Zeliang
Brucella spp. avoid host immune recognition and thus, weaken the immune response to infection. The Toll/interleukin-1 receptor (TIR) domain-containing protein (TcpB/Btp1) of Brucella spp. is thought to be involved in blocking host innate immune responses by binding to adaptors downstream of Toll-like receptors. In this study, based on the observation that TcpB binds to the host target proteins, MAL, through the TIR domain, we examined decoy peptides from TcpB TIR domains and found that TB-8 and TB-9 substantially inhibit lipopolysaccharide (LPS)-induced signaling in vitro and in vivo. Both these peptides share a common loop, the DD loop, indicating a novel structural region mediating TIR interactions. The inhibition of LPS signaling by TB-8 and TB-9 shows no preference to MyD88-dependent cytokines, such as TNF-alpha and IL-1 beta or TRIF-dependent cytokines including IFN-beta and IL-6. Furthermore, these two peptides rescue the virulence of Brucella Delta tcpB mutants at the cellular level, indicating key roles of the DD loop in Brucella pathogenesis. In conclusion, identification of inhibitors from the bacterial TIR domains is helpful not only for illustrating interacting mechanisms between TIR domains and bacterial pathogenesis, but also for developing novel signaling inhibitors and therapeutics for human inflammatory diseases. (C) 2016 Elsevier GmbH. All rights reserved.
