寡核苷酸表达谱揭示异烟肼耐药对结核分支杆菌致病性的影响

Effect of Isoniazid Resistance on Pathogenicity of Mycobacterium tuberculosis Revealed by Oligonucleotide Microarray Profiling

目的研究结核分支杆菌异烟肼耐药菌株与H37Rv异烟肼敏感菌株感染巨噬细胞后差异表达的基因。方法利用高密度cDNA芯片检测巨噬细胞U937感染结核分支杆菌异烟肼耐药菌株与H37Rv后的基因表达谱的差异。结果两者诱导巨噬细胞的差异表达基因有53条,异烟肼耐药菌株比敏感菌株诱导多种趋化因子和细胞免疫增强的细胞因子表达上调和免疫抑制细胞因子IL10等表达下调。结论异烟肼耐药对细菌毒力有明显的影响,异烟肼耐药菌株的致病力下降,异烟肼耐药菌株容易被宿主免疫系统清除;结果为耐多药结核病控制提供依据;骨桥接素和巨噬细胞趋化因子等,在抗异烟肼耐药结核分支杆菌感染免疫中的作用值得深入研究。

OBJECTIVE To investigate the effect of isoniazid resistance on the pathogenicity of Mycobacterium tuberculosis. METHODS Oligonucleotide microarray containing 16 900 genes was used to compare the gene expression profiling of macrophage U937 after exposure to isoniazid resistant M.tuberculosis and H37Rv strain. RESULTS There were exiting remarkable difference between isoniazid resistant M.tuberculosis and H37Rv strain induced gene expression in host cells. Among the 16 900 genes monitored, 53 genes were differentially expressed. Isoniazid resistant M.tuberculosis induced more expression of some chemokines and cytokines that could enhance Th1 cell mediated immune response. CONCLUSIONS The results suggest that isoniazid resistant M.tuberculosis be more easy to be killed and eliminated by host cells than H37Rv strain. Isoniazid resistance affects virulence of M.tuberculosis and provide important information for constitution of multidrug resistant tuberculosis control program.