Toll样受体4及其调控的信号通路关键因子在HIV合并马尔尼菲篮状菌感染患者单核巨噬细胞中的表达水平及临床意义

Expression levels and clinical significance of Toll-like receptor 4 and signaling pathway key factors undeRits regulation in mononuclear macrophages of HIV patients with Talaromyces marneffei infection

目的探讨Toll样受体(TLR)4及其调控的信号通路关键因子在HIV合并马尔尼菲篮状菌(T.marneffei)感染患者外周血单核巨噬细胞的表达水平及临床意义。方法将35例HIV感染者按是否合并T.marneffei感染分为合并T.marneffei感染组(15例)和单纯HIV感染组(20例)。收集两组患者的临床资料,并应用流式细胞术检测两组患者外周血单核巨噬细胞中TLR2、TLR4、TLR9的蛋白表达水平,TLR4信号通路中间因子TANK结合激酶1(TBK1)、髓样分化因子88(MyD88)、干扰素调节因子7(IRF7)的蛋白表达水平,以及下游炎症因子白细胞介素6(IL-6)、γ干扰素的蛋白表达水平。比较合并T.marneffei感染组和单纯HIV感染组间,以及CD4^(+)T淋巴细胞计数<200个/μL和CD4^(+)T淋巴细胞计数<100个/μL患者中合并T.marneffei感染组和单纯HIV感染组间上述指标的差异。结果合并T.marneffei感染组的CD4^(+)T淋巴细胞计数低于单纯HIV感染组,TLR4、MyD88、TBK1、IRF7、IL-6、γ干扰素的蛋白表达水平均高于单纯HIV感染组(均P<0.05),而两组的TLR2和TLR9蛋白表达水平差异均无统计学意义(均P>0.05)。在CD4^(+)T淋巴细胞计数<200个/μL的患者中和CD4^(+)T淋巴细胞计数<100个/μL的患者中,合并T.marneffei感染组的TLR4蛋白表达水平,TLR4信号通路中间因子TBK1、MyD88、IRF7的蛋白表达水平均高于单纯HIV感染组,且在CD4^(+)T淋巴细胞计数<200个/μL的患者中,合并T.marneffei感染组的γ干扰素蛋白表达水平高于单纯HIV感染组,在CD4^(+)T淋巴细胞计数<100个/μL的患者中,合并T.marneffei感染组的IL-6蛋白表达水平高于单纯HIV感染组(均P<0.05)。结论TLR4及其信号通路相关因子在HIV合并T.marneffei感染患者单核巨噬细胞中呈异常表达,其可能是促进HIV合并T.marneffei感染、影响HIV病程进展的因素之一。

Objective To explore the expression levels and clinical significance of Toll-like receptor(TLR)4 and TLR4-regulated signaling pathway key factors in peripheral blood mononucleaRmacrophages of HIV patients with Talaromyces marneffei(T.marneffei)infection.Methods Thirty-five HIV infectors were divided into concomitant T.marneffei infection group(15 cases)and simple HIV infection group(20 cases)according to whetheRthey were complicated with T.marneffei infection oRnot.The clinical data of patients in the two groups were collected,and multiple indices were detected in theiRperipheral blood mononucleaRmacrophages by flow cytometry,including the protein expression levels of TLR2,TLR4,and TLR9,the protein expression levels of intermediate factors such as TANK-binding kinase 1(TBK1),myeloid differentiation factoR88(MyD88)and interferon regulatory factoR7(IRF7)in the TLR4 signaling pathway,as well as the protein expression levels of downstream inflammatory factors such as interleukin 6(IL-6)andγinterferon.The aforementioned indices were compared between the concomitant T.marneffei infection group and the simple HIV infection group,and between patients with CD4^(+)T lymphocyte count<200 cells/μL oRwith CD4^(+)T lymphocyte count<100 cells/μL in the concomitant T.marneffei infection group and those in the simple HIV infection group.Results The concomitant T.marneffei infection group had a loweRCD4^(+)T lymphocyte count and higheRprotein expression levels of TLR4,MyD88,TBK1,IRF7,IL-6,andγinterferon than the simple HIV infection group(all P<0.05),whereas there was no statistically significant difference between the two groups in the protein expression level of TLR2 oRTLR9(all P>0.05).As foRpatients with CD4^(+)T lymphocyte count<200 cells/μL and patients with CD4^(+)T lymphocyte count<100 cells/μL,the concomitant T.marneffei infection group exhibited higheRprotein expression levels of TLR4 and intermediate factors in the TLR4 signaling pathway,including TBK1,MyD88,and IRF7,as compared with the simple HIV infection group;in addition,as foRpatients with CD4^(+)T lymphocyte count<200 cells/μL,the concomitant T.marneffei infection group yielded a higheRexpression level ofγinterferon protein than the simple HIV infection group,and as foRpatients with CD4^(+)T lymphocyte count<100 cells/μL,the concomitant T.marneffei infection group yielded a higheRexpression level of IL-6 protein than the simple HIV infection group(all P<0.05).Conclusion TLR4 and its signaling pathway-related factors exhibit abnormal expression in mononucleaRmacrophages of HIV patients complicated with T.marneffei infection,which may be one of the factors that promotes concomitant T.marneffei infection in HIV patients and affects the progression of HIV course.