A novel role for lipid droplets in the organismal antibacterial response.
A novel role for lipid droplets in the organismal antibacterial response.
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DOI：
10.7554/elife.00003
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发表时间：
2012-11-13
期刊：
影响因子：
7.7
通讯作者：
Gross SP
中科院分区：
文献类型：
--
作者：
Anand P;Cermelli S;Li Z;Kassan A;Bosch M;Sigua R;Huang L;Ouellette AJ;Pol A;Welte MA;Gross SP
我们以前发现组蛋白结合到胞质脂滴（LD），在这里，我们表明，这形成了一个细胞抗菌防御系统。在正常条件下，在细菌脂多糖（LPS）或脂磷壁酸（LTA）存在下，组蛋白被隔离在液滴上，从液滴中释放出来，并在体外有效杀死细菌。与液滴结合的组蛋白也在体内发挥作用：当注射到缺乏与液滴结合的组蛋白的果蝇胚胎中时，细菌迅速生长。相比之下，注入胚胎的细菌与液滴结合的组蛋白死亡。当用四种不同的细菌物种进行挑战时，具有液滴结合的组蛋白的胚胎显示出超过四倍的存活优势。我们的数据表明，这种细胞内抗菌防御系统可能在成年苍蝇中发挥作用，也可能在小鼠中发挥作用。DOI：http://dx.doi.org/10.7554/eLife.00003.001组蛋白是在大多数动物细胞中大量发现的蛋白质，它们的主要工作是帮助DNA链在细胞核内折叠成紧凑和坚固的结构。在体外，组蛋白在杀死细菌方面非常有效，并且有一些证据表明，从细胞分泌的组蛋白提供对细胞外细菌的保护。然而，许多类型的细菌能够进入细胞，在那里它们可以避开免疫系统并继续复制。原则上，组蛋白可以从内部保护细胞免受这种细菌的侵害，但多年来这被认为是不可能的，因为大多数组蛋白与细胞核中的DNA链结合，而细菌在胞质中复制。此外，游离组蛋白对细胞的破坏性极大，因此大多数物种都开发了检测和降解胞质中游离组蛋白的机制。然而，最近发现组蛋白可以与各种动物细胞和组织中的脂滴结合，脂滴是细胞质中主要用于储存能量的细胞器。现在，Anand等人已经证明，与脂滴结合的组蛋白可以保护细胞免受细菌的侵害，而不会引起任何通常与游离组蛋白存在相关的伤害。在从果蝇胚胎中纯化的脂滴的体外实验中，他们发现结合在脂滴上的组蛋白可以被释放出来杀死细菌。细菌产生的脂多糖或脂磷壁酸释放组蛋白。在体内也观察到了这种效果：使用四种不同的细菌物种，Anand等人将类似数量的细菌注入含有与脂滴结合的组蛋白的果蝇胚胎中，以及经过基因改造的胚胎中，使它们不含有这种与脂滴结合的组蛋白。虽然大多数正常胚胎存活下来，但绝大多数没有液滴结合组蛋白的胚胎死亡。在对成年苍蝇的实验中也发现了类似的结果，沿着的证据表明，组蛋白也可能为小鼠提供抵抗细菌的防御。DOI：http://dx.doi.org/10.7554/eLife.00003.002网站
We previously discovered histones bound to cytosolic lipid droplets (LDs); here we show that this forms a cellular antibacterial defense system. Sequestered on droplets under normal conditions, in the presence of bacterial lipopolysaccharide (LPS) or lipoteichoic acid (LTA), histones are released from the droplets and kill bacteria efficiently in vitro. Droplet-bound histones also function in vivo: when injected into Drosophila embryos lacking droplet-bound histones, bacteria grow rapidly. In contrast, bacteria injected into embryos with droplet-bound histones die. Embryos with droplet-bound histones displayed more than a fourfold survival advantage when challenged with four different bacterial species. Our data suggests that this intracellular antibacterial defense system may function in adult flies, and also potentially in mice. DOI: http://dx.doi.org/10.7554/eLife.00003.001 Histones are proteins found in large numbers in most animal cells, where their primary job is to help DNA strands fold into compact and robust structures inside the nucleus. In vitro, histones are very effective at killing bacteria, and there is some evidence that histones secreted from cells provide protection against bacteria living outside cells. However, many types of bacteria are able to enter cells, where they can avoid the immune system and go on to replicate. In principle histones could protect cells against such bacteria from the inside, but for many years this was thought to be unlikely because most histones are bound to DNA strands in the cell nucleus, whereas the bacteria replicate in the cytosol. Moreover, free histones can be extremely damaging to cells, so most species have developed mechanisms to detect and degrade free histones in the cytosol. Recently, however, it was discovered that histones can bind to lipid droplets—organelles in the cytosol that are primarily used to store energy—in various animal cells and tissues. Now, Anand et al. have demonstrated that histones bound to lipid droplets can protect cells against bacteria without causing any of the harm normally associated with the presence of free histones. In in vitro experiments with lipid droplets purified from Drosophila embryos, they showed that histones bound to lipid droplets could be released to kill bacteria. The histones were released by lipopolysaccharide or lipoteichoic acid produced by the bacteria. The effect was also observed in vivo: using four different bacterial species, Anand et al. injected similar numbers of bacteria into Drosophila embryos that contained histones bound to lipid droplets, and also into embryos that had been genetically modified so that they did not contain such droplet-bound histones. While most of the normal embryos survived, the vast majority of the embryos without droplet-bound histones died. Similar results were also found in experiments on adult flies, along with evidence which suggests that histones might also provide defenses against bacteria in mice. DOI: http://dx.doi.org/10.7554/eLife.00003.002
影响因子：
2.4
作者：
Senga, Fujitoshi;Yin, Li;Karasuno, Hiroshi;Ohtaki, Hirokazu;Nakamachi, Tomoya;Satoh, Kazue;Shioda, Seiji
通讯作者：
Shioda, Seiji