MiR-101-3p down-regulates TLR2 expression, leading to reduction in cytokines production by T. pallidum-stimulated macrophages

ABSTRACT 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 (miRNAs) in host immunity. We assessed whether miRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that miR-101-3p levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, while TLR2 levels were higher in syphilitic patients 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, TNF-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 up-regulated cytokines 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 up-regulates miR-101-3p expression, which in turn inhibits the TLR2 signaling pathway, leading to reduced cytokines production.