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The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL ‐8 secretion
Author(s) -
Luo Xi,
Zhang Xiaohong,
Gan Lin,
Zhou Chenglong,
Zhao Tie,
Zeng Tiebing,
Liu Shuangquan,
Xiao Yongjian,
Yu Jian,
Zhao Feijun
Publication year - 2018
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.13879
Subject(s) - biology , tlr2 , cd14 , pyroptosis , bacterial outer membrane , peripheral blood mononuclear cell , microbiology and biotechnology , innate immune system , thp1 cell line , monocyte , programmed cell death , inflammasome , apoptosis , cell culture , immune system , immunology , inflammation , in vitro , gene , biochemistry , genetics , escherichia coli
Treponema pallidum is the pathogen that causes syphilis, a sexually transmitted disease; however, the pathogenic mechanism of this organism remains unclear. Tp92 is the only T. pallidum outer membrane protein that has structural features similar to the outer membrane proteins of other Gram‐negative bacteria, but the exact functions of this protein remain unknown. In the present study, we demonstrated that the recombinant Tp92 protein can induce human mononuclear cell death. Tp92 mediated the human monocytic cell line derived from an acute monicytic leukemia patient (THP‐1) cell death by recognizing CD 14 and/or TLR 2 on cell surfaces. After the stimulation of THP ‐1 cells by the Tp92 protein, Tp92 may induce atypical pyroptosis of THP ‐1 cells via the pro‐caspase‐1 pathway. Meanwhile, this protein caused the apoptosis of THP ‐1 cells via the receptor‐interacting protein kinase 1/caspase‐8/aspase‐3 pathway. Tp92 reduced the number of monocytes among peripheral blood mononuclear cells. Interestingly, further research showed that Tp92 failed to increase the tumour necrosis factor‐α, interleukin ( IL )‐1β, IL ‐6, IL ‐10, IL ‐18 and monocyte chemotactic protein 1 (MCP)‐1 levels but slightly elevated the IL ‐8 levels via the Nuclear Factor (NF)‐κB pathway in THP ‐1 cells. The data suggest that Tp92 recognizes CD 14 and TLR 2, transfers the signal to a downstream pathway, and activates NF‐κB to mediate the production of IL ‐8. This mechanism may help T. pallidum escape recognition and elimination by the host innate immune system.

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