MicroRNA-101-3p Downregulates TLR2 Expression, Leading to Reduction in Cytokine Production by Treponema pallidum-Stimulated Macrophages

J Invest Dermatol. 2020 Aug;140(8):1566-1575.e1. doi: 10.1016/j.jid.2019.12.012. Epub 2020 Jan 11.


Treponema pallidum (Tp) infection-induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs in host immunity. We assessed whether microRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that microRNA-101-3p (miR-101-3p) levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, whereas toll-like receptor (TLR) 2 levels were higher in patients with syphilis than in healthy controls. In vitro, stimulation of THP-1 cells with Tp increased miR-101-3p expression. Moreover, miR-101-3p reduced expression levels of TLR2 mRNA and protein in THP-1 cells via binding to the 3' untranslated region of TLR2. Likewise, miR-101-3p inhibited production of inflammatory cytokines, including IL-1β, IL-6, tumor necrosis factor-α, and IL-12, in Tp-stimulated macrophages. IL-1β and IL-6 mRNA expression levels were reduced by transfection of macrophages with a TLR2-specific small interfering RNA. Conversely, overexpression of TLR2 upregulated cytokine expression. Patients with secondary syphilis exhibited the highest levels of plasma IL-6, which were negatively correlated with miR-101-3p. In conclusion, Tp infection upregulates miR-101-3p expression, which in turn inhibits the TLR2 signaling pathway, leading to reduced cytokine production.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Down-Regulation / immunology
  • Female
  • Healthy Volunteers
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interleukin-12 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Syphilis / blood
  • Syphilis / immunology*
  • Syphilis / microbiology
  • THP-1 Cells
  • Toll-Like Receptor 2 / genetics*
  • Treponema pallidum / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • MIRN101 microRNA, human
  • MicroRNAs
  • TLR2 protein, human
  • TNF protein, human
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Interleukin-12