Extracellular adenosine mediates a systemic metabolic switch during immune response.
Extracellular adenosine mediates a systemic metabolic switch during immune response.
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DOI：
10.1371/journal.pbio.1002135
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发表时间：
2015-04
期刊：
影响因子：
9.8
通讯作者：
Dolezal T
中科院分区：
文献类型：
--
作者：
Bajgar A;Kucerova K;Jonatova L;Tomcala A;Schneedorferova I;Okrouhlik J;Dolezal T
免疫防御在能量上是昂贵的，因此有效的反应需要生物体的代谢适应，以将来自储存、生长和发育的能量重新分配给免疫系统。我们采用自然感染果蝇与寄生蜂研究能量调节免疫反应。为了对抗入侵，宿主必须产生专门的免疫细胞（片状细胞）来摧毁寄生虫卵。我们发现，一个显着的一部分的营养物质分配到分化lamellocytes时，否则将用于发展。这种全身代谢开关是由免疫细胞释放的细胞外腺苷介导的。这种转换对于有效的免疫反应至关重要。阻止腺苷从免疫细胞转运或阻断腺苷受体可阻止代谢转换和发育减速，从而显著降低宿主抵抗力。因此，腺苷作为一种信号，“自私”的免疫细胞在感染期间发送，以确保更多的能量，而牺牲其他组织。一项关于果蝇对寄生蜂卵的反应的研究表明，免疫细胞自私地释放腺苷作为触发系统代谢开关的信号，从而抑制非免疫过程并为免疫活动提供能量和营养。阅读Primer。免疫反应在能量上是昂贵的，通常需要整个生物体的适应，以确保它获得足够的能量。目前还不清楚在免疫应答期间生物体内能量资源的分布是如何调节的。为了更好地理解这一点，我们用寄生蜂感染果蝇幼虫-寄主幼虫有48小时前，他们化蛹摧毁感染的“外来者”或面临破坏的寄生蜂，将消耗发展蛹。在这里，我们发现了一个信号，由宿主免疫细胞产生，它介导了系统性的能量转换。这种信号-腺苷-抑制了宿主从幼虫到蛹的发育过程，从而为免疫系统释放了能量。我们发现，果蝇幼虫的发育延迟对于有效的免疫反应至关重要;如果没有腺苷信号，对寄生虫的抵抗力就会急剧下降。免疫细胞产生的这种信号表明，在应对外部压力时，免疫系统可以动员从生物体的其他部分重新分配能量和营养物质。
Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. A study of the fruit fly's response to parasitoid wasp eggs reveals that immune cells selfishly release adenosine as a signal to trigger a systemic metabolic switch, thereby suppressing nonimmune processes and securing energy and nutrients for immune activity. Read the Primer. The immune response is energetically costly and often requires adaption of the whole organism to ensure it receives enough energy. It is not well understood how distribution of energy resources within the organism is regulated during an immune response. To understand this better, we used parasitoid wasp infection of fruit fly larvae—the host larvae have 48 h before they pupate to destroy the infecting “alien” or face destruction by the parasitoid that will consume the developing pupa. Here we find a signal, generated by the host immune cells, which mediates a systemic energy switch. This signal—adenosine—suppresses processes driving larval to pupal development of the host, thereby freeing up energy for the immune system. We show that the resulting developmental delay in the fruit fly larvae is crucial for an efficient immune response; without the adenosine signal, resistance to the parasitoid drops drastically. Generation of this signal by immune cells demonstrates that in response to external stressors, the immune system can mobilize reallocation to itself of energy and nutrients from the rest of the organism.
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影响因子：
7.7
作者：
Figler RA;Wang G;Srinivasan S;Jung DY;Zhang Z;Pankow JS;Ravid K;Fredholm B;Hedrick CC;Rich SS;Kim JK;LaNoue KF;Linden J
通讯作者：
Linden J
DOI：
10.1523/jneurosci.1240-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jinka TR;Tøien Ø;Drew KL
通讯作者：
Drew KL
影响因子：
3.8
作者：
Dolezelova, Eva;Nothacker, Hans-Peter;Zurovec, Michal
通讯作者：
Zurovec, Michal
影响因子：
7.7
作者：
Faulhaber-Walter, Robert;Jou, William;Schnermann, Jurgen B.
通讯作者：
Schnermann, Jurgen B.
影响因子：
4.5
作者：
Hull-Thompson J;Muffat J;Sanchez D;Walker DW;Benzer S;Ganfornina MD;Jasper H
通讯作者：
Jasper H