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Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway

Man Xu1, Yafeng Xie2, Chuanhao Jiang3

  • 1Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.

Immunobiology
|January 28, 2017
PubMed

Insights

Treponema pallidum flagellins stimulate interleukin (IL)-6 and IL-8 production in human monocytes. This process involves Toll-like receptor 5 (TLR5) and the MAPK/NF-κB signaling pathways, crucial for understanding syphilis pathogenesis.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Syphilis pathogenesis involves tissue damage potentially linked to inflammation, but Treponema pallidum virulence factors and cytokine induction mechanisms remain unclear.
  • Flagellin, a pathogen-associated molecular pattern (PAMP), is known to be a potent immunogen that triggers inflammatory responses.

Purpose of the Study:

  • To investigate the role of Treponema pallidum flagellins in inducing pro-inflammatory cytokine production in human monocytes.
  • To elucidate the molecular signaling pathways, including Toll-like receptor 5 (TLR5), MyD88, mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB), involved in this response.

Main Methods:

  • Human monocytes were stimulated with Treponema pallidum flagellins (FlaB1, FlaB2, FlaB3).
  • Gene silencing of TLR5 and MyD88 (using small interfering RNA and dominant-negative plasmid, respectively) was employed.
  • Western Blot and immunofluorescence assays were used to assess the involvement of MAPK (ERK, p38) and NF-κB signaling pathways.

Main Results:

  • Treponema pallidum flagellins significantly upregulated the production of interleukin (IL)-6 and IL-8 in human monocytes.
  • Silencing TLR5 or MyD88 abrogated flagellin-induced IL-6 and IL-8 expression.
  • Flagellin-mediated IL-6 and IL-8 production was dependent on ERK, p38, and NF-κB signaling, as confirmed by inhibition studies.

Conclusions:

  • Treponema pallidum flagellins induce IL-6 and IL-8 production through the TLR5 and MAPK/NF-κB signaling pathways in THP-1 cells.
  • These findings enhance the understanding of the molecular mechanisms underlying Treponema pallidum-induced inflammation and pathogenesis.
Keywords:
FlagellinHuman monocytesInflammationTLR5 signalingTreponema pallidum

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