Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
J Cell Sci. 2010 Feb 15;123(Pt 4):627-33. doi: 10.1242/jcs.060731.
Survival of all animals depends on effective protection against infection. In Drosophila, opportunistic infection kills larvae if they lack the Rel/NF-kappaB proteins Dorsal and Dif. We have used tissue-specific expression of Dif and Dorsal to reveal that these Rel proteins act in three different tissues to defend larvae from infection. Dif and Dorsal act in circulating blood cells, where they are required autonomously to promote blood-cell survival and phagocytosis of microorganisms. We show that a major transcriptional target of Dorsal and Dif in blood cells is Drosophila IAP1, a gene protecting these cells from death. We find that in addition to their autonomous role in blood-cell survival, Dif and Dorsal also act in the fat body to produce factors that promote blood-cell viability. These Rel proteins act in the epidermis to prevent infection by maintaining a barrier to microbial entry. Dorsal or Dif in any one of the three tissues is sufficient to defend the animal from opportunistic infection. Thus Drosophila has a multi-pronged system of defense and each branch of this network requires Rel proteins. Based on similarities between Drosophila and mammals, we propose that a Rel-dependent network is an ancient and robust framework of animal immune systems.
所有动物的生存都依赖于有效预防感染。在果蝇中，机会性感染如果幼虫缺乏 Rel/NF-κB 蛋白 Dorsal 和 Dif，就会杀死幼虫。我们利用 Dif 和 Dorsal 的组织特异性表达，揭示了这些 Rel 蛋白在三种不同组织中发挥作用，以保护幼虫免受感染。Dif 和 Dorsal 在循环血细胞中发挥作用，在这些细胞中，它们需要自主作用以促进血细胞的存活和微生物的吞噬作用。我们表明，Dorsal 和 Dif 在血细胞中的一个主要转录靶标是 Drosophila IAP1，这是一种保护这些细胞免受死亡的基因。我们发现，Dif 和 Dorsal 除了在血细胞存活中具有自主作用外，还在脂肪体中发挥作用，产生促进血细胞活力的因子。这些 Rel 蛋白在表皮中发挥作用，通过维持微生物进入的屏障来防止感染。在这三种组织中的任何一种组织中，Dorsal 或 Dif 都足以保护动物免受机会性感染。因此，果蝇具有多方面的防御系统，这个网络的每个分支都需要 Rel 蛋白。基于果蝇和哺乳动物之间的相似性，我们提出依赖于 Rel 的网络是动物免疫系统的一个古老而强大的框架。
