MiR-101-3p靶向TLR2-MALAT1轴抑制M1型巨噬细胞极化介导梅毒免疫逃逸

梅毒螺旋体（Tp）能够免疫逃逸形成潜伏感染继而引发更严重的损伤（如神经梅毒）。但是目前Tp免疫逃逸的机制尚不清晰。已有研究指出巨噬细胞在清除Tp过程中发挥重要作用，但尚不清楚Tp能否通过影响巨噬细胞功能介导免疫逃逸。本项目前期研究表明Tp能够诱导巨噬细胞miR-101-3p上调，进一步研究发现miR-101-3p抑制巨噬细胞M1型极化；生信分析发现miR-101-3p靶向极化相关分子TLR2-MALAT1。据此我们提出假设：Tp能够诱导巨噬细胞miR-101-3p上调，靶向TLR2-MALAT1轴抑制M1巨噬细胞极化及其功能，从而介导免疫逃逸。本项目将在临床样本中研究miR-101-3p、巨噬细胞极化与梅毒的关联，进而在细胞模型研究miR-101-3p调控极化的机制，并在动物模型和临床标本中进行验证。本项目为解释梅毒螺旋体如何免疫逃逸提供了新的理论基础，为梅毒的治疗提供了新的分子靶标。

Treponema pallidum (Tp) immune evasion leads to latent infection, which can cause more serious damage (such as neurosyphilis). At present, the mechanism of Tp immune escape is still unclear. Macrophages play an important role in Tp clearance. However, whether Tp can mediate immune escape by inhibiting the function of macrophages is not yet known. Previous studies have shown that Tp can induce the up-regulation of miR-101-3p in macrophages, and miR-101-3p inhibits the M1 macrophages polarization. Bioinformatics analysis suggests that miR-101-3p targets polarization-related molecule TLR2-MALAT1. Therefore, we hypothesize that Tp can induce the up-regulation of miR-101-3p in macrophages, and target the TLR2-MALAT1 axis to inhibit the polarization and function of M1 macrophages, thereby mediating immune escape. This project will first study the relationship between miR-101-3p, macrophage polarization and syphilis in clinical samples. Then study the mechanism of miR-101-3p regulating polarization in a cell model. Finally, the molecular mechanism was verified in animal models and clinical specimens. This project provides a new theoretical basis for explaining how Treponema pallidum escapes from immunity and provides a new molecular target for the treatment of syphilis.