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非典型分枝杆菌(包括鸟分枝杆菌和蟾分枝杆菌)的 cord 因子可刺激与肺结核有关的某些促炎细胞因子的分泌。

Cord factors from atypical mycobacteria (Mycobacterium alvei, Mycobacterium brumae) stimulate the secretion of some pro-inflammatory cytokines of relevance in tuberculosis.

机构信息

Departamento de Genética y Microbiología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.

SAI, Universidad de Murcia, Murcia, Spain.

出版信息

Microbiology (Reading). 2012 Nov;158(Pt 11):2878-2885. doi: 10.1099/mic.0.060681-0. Epub 2012 Sep 13.

DOI:10.1099/mic.0.060681-0
PMID:22977091
Abstract

The ability to induce several cytokines relevant to tuberculosis (TNF-α, IL-1β, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from Mycobacterium alvei CR-21(T) and Mycobacterium brumae CR-270(T) was studied in the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor from Mycobacterium tuberculosis H37Rv, where this glycolipid appears to be implicated in the pathogenesis of tuberculosis. Details of the fine structure of these molecules were obtained by NMR and MS. The mycoloyl residues were identified as α and (ω-1)-methoxy in M. alvei CR-21(T) and α in M. brumae CR-270(T); in both cases they were di-unsaturated instead of cyclopropanated as found in M. tuberculosis. In RAW 264.7 cells, cord factors from M. alvei CR-21(T), M. brumae CR-270(T) and M. tuberculosis differed in their ability to stimulate IL-6, the higher levels corresponding to the cord factor from M. tuberculosis. In THP-1 cells, a similar overall profile of cytokines was found for M. alvei CR-21(T) and M. brumae CR-270(T), with high proportions of IL-1β and TNF-α, and different from M. tuberculosis, where IL-6 and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria M. alvei CR-21(T) and M. brumae CR-270(T) stimulated the secretion of several pro-inflammatory cytokines, although there were some differences with those of M. tuberculosis H37Rv. This finding seems to be due to their particular mycoloyl substituents and could be of interest when considering the potential adjuvanticity of these molecules.

摘要

研究了来自肺泡分枝杆菌 CR-21(T)和布鲁氏分枝杆菌 CR-270(T)的 cord 因子(海藻糖二霉菌酸酯)诱导与肺结核相关的几种细胞因子(TNF-α、IL-1β、IL-6、IL-12p40 和 IL-23)的能力,并与来自结核分枝杆菌 H37Rv 的 cord 因子进行了比较,该脂糖似乎与肺结核的发病机制有关。通过 NMR 和 MS 获得了这些分子的精细结构细节。Mycoloyl 残基被鉴定为 M. alvei CR-21(T)中的α和(ω-1)-甲氧基和 M. brumae CR-270(T)中的α;在这两种情况下,它们都是二不饱和的,而不是像在结核分枝杆菌中那样环丙烷化。在 RAW 264.7 细胞中,来自 M. alvei CR-21(T)、M. brumae CR-270(T)和 M. tuberculosis 的 cord 因子在刺激 IL-6 的能力上有所不同,较高的水平对应于来自 M. tuberculosis 的 cord 因子。在 THP-1 细胞中,M. alvei CR-21(T)和 M. brumae CR-270(T)的细胞因子总体谱相似,IL-1β 和 TNF-α的比例较高,与 M. tuberculosis 不同,M. tuberculosis 中 IL-6 和 IL-12p40 占主导地位。获得的数据表明,来自非典型分枝杆菌 M. alvei CR-21(T)和 M. brumae CR-270(T)的 cord 因子刺激了几种促炎细胞因子的分泌,尽管与 M. tuberculosis H37Rv 相比存在一些差异。这一发现似乎归因于它们特殊的 mycoloyl 取代基,当考虑这些分子的潜在佐剂活性时,这可能是有意义的。

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