Drosophila innate immunity: regional and functional specialization of prophenoloxidases.
Drosophila innate immunity: regional and functional specialization of prophenoloxidases.
复制标题
果蝇先天免疫：酚氧化酶原的区域和功能专业化。
DOI：
10.1186/s12915-015-0193-6
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发表时间：
2015-10-01
期刊：
影响因子：
5.4
通讯作者：
Lemaitre B
中科院分区：
文献类型：
--
作者：
Dudzic JP;Kondo S;Ueda R;Bergman CM;Lemaitre B
进化过程中免疫系统的多样化涉及特定门中特定基因家族的扩展。为了更好地理解后生动物免疫系统，需要分析这种免疫基因扩增背后的逻辑。由于我们可以轻松地在生物体中产生多个突变，因此这种分析现在已经可以实现。在本文中，我们通过产生单、双和三突变体来分析三种果蝇酚氧化酶原（PPO）对宿主防御的贡献。 PPO 是催化感染部位和寄生虫周围黑色素产生的酶。它们是促进黑色化反应的限速酶，黑色化反应是节肢动物的主要免疫机制。昆虫中 PPO 编码基因的数量各不相同，从蜜蜂的 1 个到蚊子的 10 个不等。通过单独和组合分析突变，我们为果蝇的三个 PPO 中的每一个赋予了特定的功能。我们的研究证实，在脓毒症或清洁性损伤时，晶体细胞产生的两种 PPO（PPO1 和 PPO2）会导致血淋巴中的大部分黑色化。相比之下，PPO3（一种仅限于黑腹果蝇群体的 PPO）在层状细胞中表达，并在包封过程中促进黑化。有趣的是，另一组重叠的 PPO（PPO2 和 PPO3）在寄生蜂感染后实现了荚膜的黑色化。使用单个或组合突变使我们能够证明每个 PPO 突变体都有特定的表型，并且需要敲除三个基因中的两个才能完全消除特定功能。因此，果蝇 PPO 具有部分重叠的功能，可以在至少两种情况下优化黑化：损伤后或封装期间。由于 PPO3 仅限于黑腹果蝇群体，这表明片状细胞产生的 PPO 已成为对抗寄生蜂的最新防御机制。我们得出的结论是，空间定位、即时或后期可用性以及激活模式的差异是三种果蝇 PPO 功能多样化的基础，其中每种 PPO 都具有非冗余但重叠的功能。本文的在线版本 (doi:10.1186/s12915-015-0193-6) 包含补充材料，可供授权用户使用。
The diversification of immune systems during evolution involves the expansion of particular gene families in given phyla. A better understanding of the metazoan immune system requires an analysis of the logic underlying such immune gene amplification. This analysis is now within reach due to the ease with which we can generate multiple mutations in an organism. In this paper, we analyze the contribution of the three Drosophila prophenoloxidases (PPOs) to host defense by generating single, double and triple mutants. PPOs are enzymes that catalyze the production of melanin at the site of infection and around parasites. They are the rate-limiting enzymes that contribute to the melanization reaction, a major immune mechanism of arthropods. The number of PPO-encoding genes is variable among insects, ranging from one in the bee to ten in the mosquito. By analyzing mutations alone and in combination, we ascribe a specific function to each of the three PPOs of Drosophila. Our study confirms that two PPOs produced by crystal cells, PPO1 and PPO2, contribute to the bulk of melanization in the hemolymph, upon septic or clean injury. In contrast, PPO3, a PPO restricted to the D. melanogaster group, is expressed in lamellocytes and contributes to melanization during the encapsulation process. Interestingly, another overlapping set of PPOs, PPO2 and PPO3, achieve melanization of the capsule upon parasitoid wasp infection. The use of single or combined mutations allowed us to show that each PPO mutant has a specific phenotype, and that knocking out two of three genes is required to abolish fully a particular function. Thus, Drosophila PPOs have partially overlapping functions to optimize melanization in at least two conditions: following injury or during encapsulation. Since PPO3 is restricted to the D. melanogaster group, this suggests that production of PPO by lamellocytes emerged as a recent defense mechanism against parasitoid wasps. We conclude that differences in spatial localization, immediate or late availability, and mode of activation underlie the functional diversification of the three Drosophila PPOs, with each of them having non-redundant but overlapping functions. The online version of this article (doi:10.1186/s12915-015-0193-6) contains supplementary material, which is available to authorized users.