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The N‐terminal D1 domain of Treponema pallidum flagellin binding to TLR5 is required but not sufficient in activation of TLR5
Author(s) -
Xu Man,
Xie Yafeng,
Tan Manyi,
Zheng Kang,
Xiao Yongjian,
Jiang Chuanhao,
Zhao Feijun,
Zeng Tiebing,
Wu Yimou
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14617
Subject(s) - tlr5 , treponema , flagellin , biology , homology modeling , microbiology and biotechnology , virology , genetics , gene , syphilis , immune system , biochemistry , enzyme , innate immune system , toll like receptor , human immunodeficiency virus (hiv)
Syphilis is a chronic bacterial infection caused by Treponema pallidum ( T pallidum ) and the pathogenesis that T pallidum infection induces immunopathological damages in skin and other tissues remains unclear. We have previously reported that recombinant flagellins of T pallidum can 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 that Tp flagellins 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 ( Tp flagellins R89) of the ND1 domain and its adjacent residues ( Tp flagellins L93 and E113) constitute a hot spot that elicits IL‐6, IL‐8 transcriptions and TLR5 activation, and affects the binding of Tp flagellins to TLR5. Taken together, these results give insight into the pathogenesis of T pallidum and may contribute to the future design of Tp flagellins‐based therapeutics and syphilis vaccine.

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