Copper redistribution in murine macrophages in response to Salmonella infection
Copper redistribution in murine macrophages in response to Salmonella infection
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DOI：
10.1042/bj20112180
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发表时间：
2012-05-15
影响因子：
4.1
通讯作者：
McEwan, Alastair G.
中科院分区：
文献类型：
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作者：
Achard, Maud E. S.;Stafford, Sian L.;McEwan, Alastair G.
关键过渡金属离子的移动被认为在巨噬细胞与细胞内病原体的相互作用中至关重要。本研究调查了铜在小鼠巨噬细胞对鼠伤寒沙门氏菌反应中的作用。铜螯合剂BCS（二磺酸二亚铜，二钠盐）在感染后24小时增加了鼠伤寒沙门氏菌在原代小鼠骨髓来源巨噬细胞（BMM）内的存活，这意味着铜有助于宿主对这种病原体的有效防御。用鼠伤寒沙门氏菌感染BMM或用Toll样受体4配体脂多糖（LPS）处理，诱导了几个编码参与铜转运的蛋白质的基因[铜转运蛋白1（Ctr1）、铜转运蛋白2（Ctr2）和铜转运ATP酶1（Atp7a）]以及多铜氧化酶血浆铜蓝蛋白（Cp）的表达。LPS和鼠伤寒沙门氏菌感染都触发了BMM内点状细胞内囊泡（铜“热点”）中的铜积累，如荧光报告分子CS1（铜传感器1）所示。这些铜热点在刺激后约18小时积累达到峰值，并且依赖于细胞对铜的摄取。定位研究表明，铜热点位于与含沙门氏菌的液泡和溶酶体不同的离散囊泡中。我们提出铜热点的形成有助于针对专职细胞内细菌病原体的抗菌反应。
The movement of key transition metal ions is recognized to be of critical importance in the interaction between macrophages and intracellular pathogens. The present study investigated the role of copper in mouse macrophage responses to Salmonella enterica sv. Typhimurium. The copper chelator BCS (bathocuproinedisulfonic acid, disodium salt) increased intracellular survival of S. Typhimurium within primary mouse BMM (bone-marrow-derived macrophages) at 24 h post-infection, implying that copper contributed to effective host defence against this pathogen. Infection of BMM with S. Typhimurium or treatment with the TLR (Toll-like receptor) 4 ligand LPS (lipopolysaccharide) induced the expression of several genes encoding proteins involved in copper transport [Ctr (copper transporter) I, Ctr2 and Atp7a (copper-transporting ATPase I)], as well as the multi-copper oxidase Cp (caeruloplasmin). Both LPS and infection with S. Typhirnurium triggered copper accumulation within punctate intracellular vesicles (copper 'hot spots') in BMM as indicated by the fluorescent reporter CS 1 (copper sensor 1). These copper hot spots peaked in their accumulation at approximately 18 h post-stimulation and were dependent on copper uptake into cells. Localization studies indicated that the copper hot spots were in discrete vesicles distinct from Salmonella containing vacuoles and lysosomes. We propose that copper hot spot formation contributes to antimicrobial responses against professional intracellular bacterial pathogens.