基于SOCS1-TLR2信号通路探讨HIV/结核分枝杆菌合并感染的发病机制

林雪; 廖艳研; 潘沛江; 王建; 钟伟月; 叶力; 梁浩

doi:10.16190/j.cnki.45-1211/r.2023.12.002

基于SOCS1-TLR2信号通路探讨HIV/结核分枝杆菌合并感染的发病机制

Exploration of the pathogenesis of HIV/Mtb co-infection based on SOCS1-TLR2 signaling pathway

摘要

摘要: 目的：探讨巨噬细胞的细胞因子信号传导抑制因子1（SOCS1）-Toll样受体2（TLR2）信号通路在人免疫缺陷病毒（HIV）促进结核分枝杆菌（Mtb）感染中的作用机制。方法：采集HIV-1单感染者、Mtb单感染者、HIV-1/Mtb合并感染者和健康对照者的外周静脉血，分离外周血单个核细胞（PBMCs），流式细胞术检测PBMCs中单核巨噬细胞的SOCS1、TLR2及下游Mtb感染相关因子表达。基于巨噬细胞—HIV—Mtb感染模型，探讨SOCS1-TLR2在HIV促进Mtb感染中的作用。结果：与健康对照组相比，HIV-1单感染组、Mtb单感染组和HIV-1/Mtb合并感染组中白细胞介素（IL）-6、IL-10蛋白表达水平升高（P<0.05）；Mtb单感染组IL-1β、IL-12和干扰素（IFN）-γ蛋白表达水平升高（P<0.05）。体外细胞实验中，与对照组相比，HIV-1单感染组、Mtb单感染组和HIV-1/Mtb合并感染组中SOCS1 mRNA表达水平升高（P<0.05）；与对照组相比，HIV-1单感染组和HIV-1/Mtb合并感染组TLR2 mRNA表达水平下降（P<0.05）。构建过表达SOCS1的感染组别后，与对照组相比，HIV-1单感染组和HIV-1/Mtb合并感染组中SOCS1、IL-6表达水平升高（P<0.05），加入TLR2激动剂后，HIV-1/Mtb合并感染组中SOCS1、IL-6表达水平下降（P<0.05）。过表达SOCS1的HIV/Mtb合并感染组Mtb菌落计数最高（P<0.05）。结论：HIV-1可能通过促进SOCS1-TLR2信号通路中促Mtb感染因子IL-6和IL-10的高表达，从而利于Mtb的感染。

Abstract: Objective: To investigate the role of suppressor of cytokine signaling 1(SOCS1)-toll-like receptor 2(TLR2) signaling pathway in macrophages in the promotion of Mycobacterium tuberculosis(Mtb) infection by human immunodeficiency virus(HIV). Methods: Peripheral venous blood was collected from HIV-1 mono-infection patients, Mtb mono-infection patients, HIV-1/Mtb co-infection patients and healthy controls, and peripheral blood mononuclear cells(PBMCs) were isolated, and the expression levels of SOCS1, TLR2 and downstream Mtb infection-related factors in mononuclear macrophages in PBMCs were detected by flow cytometry. Based on the macrophage-HIV-Mtb infection model, the role of SOCS1-TLR2 in HIV-promoted Mtb infection was explored. Results: Compared with the healthy control group, the protein expression levels of interleukin(IL)-6, IL-10 were increased in the HIV-1 mono-infection group, Mtb mono-infection group and HIV-1/Mtb co-infection group(P<0.05) and the protein expression levels of IL-1β, IL-12 and interferon(IFN)-γ were increased in the Mtb mono-infection group(P<0.05). In vitro cell experiments, compared with the control group, the expression levels of SOCS1 mRNA in the HIV-1 mono-infection group, Mtb mono-infection group and HIV-1/Mtb co-infection group were increased(P<0.05), and the expression levels of TLR2 mRNA in the HIV-1 mono-infection group and HIV-1/Mtb co-infection group were decreased(P<0.05). After constructing an infection group with overexpressed SOCS1, compared with the control group, the expression levels of SOCS1 and IL-6 in the HIV-1 mono-infection group and the HIV-1/Mtb co-infection group were increased(P<0.05) and the expression levels of SOCS1 and IL-6 in the HIV-1/Mtb co-infection group were decreased after the TLR2 agonist was added(P<0.05). HIV/Mtb co-infection group with overexpressed SOCS1 had the highest Mtb colony count(P<0.05). Conclusion: HIV-1 may facilitate Mtb infection by promoting the high expression of inflammatory cytokines IL-6 and IL-10 in the SOCS1-TLR2 signaling pathway.

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