Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections
Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections
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DOI：
10.1371/journal.pone.0004490
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发表时间：
2009-02-16
期刊：
影响因子：
3.7
通讯作者：
Ligoxygakis, Petros
中科院分区：
文献类型：
--
作者：
Brown, Anthony E.;Baumbach, Janina;Ligoxygakis, Petros
背景：原发性免疫缺陷是一种先天性免疫缺陷，可导致危及生命的疾病。这些倾向描述了自然的人类免疫，并强调了toll - il -1受体-核因子κ B （tir - nf - κ B）途径组分的重要功能。由于TIR-NF-kappa B回路是高等动物宿主防御的一个保守组成部分，基因可处理的模型可能为临床干预提供思路。方法/主要发现：我们使用免疫缺陷果蝇（黑腹果蝇）来解决与细菌感染后生存有关的问题。我们在这里描述了缺乏NF-kappa B蛋白的果蝇，这是对抗革兰氏阴性细菌必不可少的，当在免疫攻击之前进行饮食短期饥饿（STS）时，它们对这种感染的存活率大大提高。STS诱导一氧化氮（NO）的释放，一氧化氮是一种在果蝇、小鼠和人类体内对抗病原体的有效分子。给予NO合成酶抑制精氨酸类似物n -硝基- l-精氨酸甲基酯（L-NAME）而不给予其无活性对映体D-NAME，再次增加了对感染的敏感性，达到了调味突变体的预期水平。令人惊讶的是，NO信号需要nf - κ B蛋白Dif，通常需要对革兰氏阳性细菌的反应。结论/意义：我们的研究结果表明，通过STS释放NO可能反映了一个进化保守过程。此外，STS可以用于解决与感染相关的免疫表型，并可能提供增强自然免疫力的方法。
Background: Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositions describe human immunity in natura and highlight the important function of components of the Toll-IL-1-receptor-nuclear factor kappa B (TIR-NF-kappa B) pathway. Since the TIR-NF-kappa B circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions.Methodology/Principal Findings: We used immunodeficient fruit flies (Drosophila melanogaster) to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-kappa B protein Relish, indispensable for countering Gram-negative bacteria, had a greatly improved survival to such infections when subject to dietary short-term starvation (STS) prior to immune challenge. STS induced the release of Nitric Oxide (NO), a potent molecule against pathogens in flies, mice and humans. Administering the NO Synthase-inhibitory arginine analog N-Nitro-L-Arginine-Methyl-Ester (L-NAME) but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levels expected for relish mutants. Surprisingly, NO signalling required the NF-kappa B protein Dif, usually needed for responses against Gram-positive bacteria.Conclusions/Significance: Our results show that NO release through STS may reflect an evolutionary conserved process. Moreover, STS could be explored to address immune phenotypes related to infection and may offer ways to boost natural immunity.