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

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。

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-infec-tion 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 ex-plored.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)-γwere 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-in-fection 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 de-creased(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-infec-tion 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 overex-pressed 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.