Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium aviuum in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis
Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium aviuum in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis
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DOI：
10.1128/iai.01196-13
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发表时间：
2014-02-01
影响因子：
3.1
通讯作者：
de Chastellier, Chantal
中科院分区：
文献类型：
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作者：
Caire-Braendli, Irene;Papadopoulos, Alexia;de Chastellier, Chantal
在结核病的休眠期，结核分枝杆菌通过驻留在泡沫状巨噬细胞（FM）中而在肺肉芽肿中持续存在，泡沫状巨噬细胞（FM）在其细胞质中含有丰富的脂质体（LB），允许杆菌将脂质积累为胞质内脂质内含物（ILI）。FM的实验模型，其中骨髓衍生的小鼠巨噬细胞感染M。并暴露于极低密度脂蛋白（VLDL）作为脂质来源。详细的电子显微镜观察的定量分析显示了以下结果。(i)巨噬细胞变成泡沫状，分枝杆菌形成ILI，宿主甘油三酯而不是胆固醇是必需的。(ii)脂质转移通过分枝杆菌诱导的LB和吞噬体之间的融合发生。(iii)分枝杆菌表现出变薄的细胞壁，变得细长，但不分裂。(iv)在去除VLDL后，LB和ILI在数小时内下降，并且分枝杆菌分裂的同时恢复使分枝杆菌的数量恢复到与未处理的对照巨噬细胞中发现的相同水平。这表明ILI的存在导致可逆的分裂阻断，而不会引起分枝杆菌复制率的变化。ILI之间的波动部分或全部延伸到整个分枝杆菌细胞质提示细菌细胞周期事件。我们建议，极低密度脂蛋白驱动的FM构成了一个明确的细胞系统，在其中研究细胞内分枝杆菌的代谢状态变化，这可能与结核病的持久性和再活化有关。
During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intracytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very-low-density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results. (i) Macrophages became foamy, and mycobacteria formed ILI, for which host triacylglycerides, rather than cholesterol, was essential. (ii) Lipid transfer occurred via mycobacterium-induced fusion between LB and phagosomes. (iii) Mycobacteria showed a thinned cell wall and became elongated but did not divide. (iv) Upon removal of VLDL, LB and ILI declined within hours, and simultaneous resumption of mycobacterial division restored the number of mycobacteria to the same level as that found in untreated control macrophages. This showed that the presence of ILI resulted in a reversible block of division without causing a change in the mycobacterial replication rate. Fluctuation between ILI either partially or fully extending throughout the mycobacterial cytoplasm was suggestive of bacterial cell cycle events. We propose that VLDL-driven FM constitute a well-defined cellular system in which to study changed metabolic states of intracellular mycobacteria that may relate to persistence and reactivation of tuberculosis.