The N-terminal D1 domain of Treponema pallidum flagellin binding to TLR5 is required but not sufficient in activation of TLR5
The N-terminal D1 domain of Treponema pallidum flagellin binding to TLR5 is required but not sufficient in activation of TLR5
复制标题
梅毒螺旋体鞭毛蛋白的 N 末端 D1 结构域与 TLR5 结合是必需的，但不足以激活 TLR5
DOI：
10.1111/jcmm.14617
复制
发表时间：
2019
影响因子：
5.3
通讯作者：
Wu Y.
中科院分区：
文献类型：
--
作者：
Xu M.;Xie Y.;Tan M.;Zheng K.;Xiao Y.;Jiang C.;Zhao F.;Zeng T.;Wu Y.
Syphilis is a chronic bacterial infection caused byTreponema pallidum(T pallidum) and the pathogenesis thatT palliduminfection induces immunopathological damages in skin and other tissues remains unclear. We have previously reported that recombinant flagellins ofT pallidumcan elicit IL‐6 and IL‐8 transcriptions via TLR5 pathway. To identify the domains which induced the pro‐inflammatory activity and the importance of the interactions between TLR5 and domains, homology‐based modelling and comparative structural analyses revealed thatTpflagellins can combine with TLR5 directly. Deletion mutations showed that the ND1 domain binding to TLR5 is required but not sufficient in TLR5 activation. Moreover, site‐directed mutagenesis analysis indicated that the arginine residue (Tpflagellins R89) of the ND1 domain and its adjacent residues (Tpflagellins L93 and E113) constitute a hot spot that elicits IL‐6, IL‐8 transcriptions and TLR5 activation, and affects the binding ofTpflagellins to TLR5. Taken together, these results give insight into the pathogenesis ofT pallidumand may contribute to the future design ofTpflagellins‐based therapeutics and syphilis vaccine.
