分枝杆菌感染巨噬细胞中miRNA表达谱及其功能

Expression profile and function of miRNAs in macrophages infected with Mycobacterium

结核分枝杆菌与宿主细胞的相互作用及对宿主的某些信号通路调节与其在巨噬细胞内保持潜伏有关。microRNAs(miRNAs)可以调控基因表达,调节机体的许多生物功能,在细菌感染中发挥调节作用。但是,宿主的miRNA是否也参与结核分枝杆菌感染尚未深入研究。本研究将致病性结核分枝杆菌H37Rv和低毒株H37Ra感染巨噬细胞,通过鉴定感染后宿主细胞中miRNA的表达谱,发现在强致病性H37Rv株(Rv)、H37Rv灭活株(Rv-)和低致病H37Ra(Ra)株分别感染人巨噬细胞THP-1中有17种miRNA的表达水平发生显著性变化(P<0.05),表明宿主miRNA可能参与结核分枝杆菌−宿主的相互作用。同时,发现了10种miRNA在致病性和非致病性结核分枝杆菌感染的细胞中存在显著差异,提示宿主miRNA可能在结核分枝杆菌的致病性和细胞内生存中发挥重要作用。进一步研究发现,miR-449a、miR-502-5p和miR-708在海分枝杆菌感染的细胞中下调,过表达这3种miRNA后的细胞对海分枝杆菌的生长具有明显抑制作用,表明miRNA在宿主与分枝杆菌的相互作用中发挥重要作用。本研究为结核分枝杆菌致病性机制及治疗结核病方法提供新思路。

The interaction between Mycobacterium tuberculosis and host,as well as the regulation of some signaling pathways in the host,were involved in pathogen latency in macrophages.microRNAs(miRNAs)regulate the gene expression and biological functions,indicating that miRNAs played a regulatory role in bacterial infections.However,whether the host's miRNAs were also involved in the process of Mycobacterium tuberculosis infection had not been thoroughly studied.This study infected macrophages with pathogenic Mycobacterium tuberculosis strain H37Rv and low virulence strain H37Ra to explore the functional miRNAs.By identifying the expression profile of miRNAs in host cells after infection,the expression of 17 miRNAs significantly changed(P<0.05)in the human macrophage THP-1 infected with highly pathogenic H37Rv strain(Rv),H37Rv inactivated strain(Rv-),and non-pathogenic H37Ra(Ra)strains respectively,indicating that host miRNAs may be involved in the interaction of Mycobacterium tuberculosis and host.Meanwhile,10 types of miRNAs showed significant differences in cells infected with pathogenic and non-pathogenic Mycobacterium tuberculosis,suggesting that host miRNAs may play an important role in the pathogenicity and intracellular survival of Mycobacterium tuberculosis.Further study had found that miR-449a,miR-502-5p,and miR-708 were downregulated in cells infected with Mycobacterium marinum.Overexpression of these three miRNAs displayed the significant inhibitory effect on the growth of Mycobacterium marinum,indicating that miRNAs played a pivotal role in the interaction between the host and Mycobacterium marinum.This study provided the new insights into the pathogenesis of Mycobacterium tuberculosis and the treatment of tuberculosis.