Regulation of DUOX by the Gαq-Phospholipase Cβ-Ca2+ Pathway in Drosophila Gut Immunity
Regulation of DUOX by the Gαq-Phospholipase Cβ-Ca2+ Pathway in Drosophila Gut Immunity
复制标题
DOI：
10.1016/j.devcel.2008.12.015
复制
发表时间：
2009-03-17
影响因子：
11.8
通讯作者：
Lee, Won-Jae
中科院分区：
文献类型：
--
作者：
Ha, Eun-Mi;Lee, Kyung-Ah;Lee, Won-Jae
所有后生动物的肠道都与各种食源性微生物不断接触。然而，宿主调节肠道微生物相互作用的信号机制尚不清楚。在这里，我们表明，磷脂酶C-β（PLC β）信号调节双氧化酶（DUOX）的活性，产生杀菌活性氧（ROS）的正常主机生存所必需的。肠道-微生物接触通过G α q快速激活PLC β，这反过来又通过肌醇1，4，5-三磷酸生成动员细胞内Ca 2+，用于DUOX依赖性ROS产生。PLC β突变果蝇的寿命很短，这是由于肠道中一种重要的营养微生物酿酒酵母（Saccharomyces cerevisiae）的繁殖不受控制。肠道特异性PLC β的重新引入恢复了有效的DUOX依赖性微生物消除能力和正常的宿主存活。这些结果表明，G α q-PLC β-Ca 2 +_ DUOX-ROS信号传导途径作为真正的第一道防线，使肠道上皮细胞能够在果蝇生命周期中动态控制酵母。
All metazoan guts are in constant contact with diverse food-borne microorganisms. The signaling mechanisms by which the host regulates gut-microbe interactions, however, are not yet clear. Here, we show that phospholipase C-beta (PLC beta) signaling modulates dual oxidase (DUOX) activity to produce microbicidal reactive oxygen species (ROS) essential for normal host survival. Gut-microbe contact rapidly activates PLC beta through G alpha q, which in turn mobilizes intracellular Ca2+ through inositol 1,4,5-trisphosphate generation for DUOX-dependent ROS production. PLC beta mutant flies had a short life span due to the uncontrolled propagation of an essential nutritional microbe, Saccharomyces cerevisiae, in the gut. Gut-specific reintroduction of the PLC beta restored efficient DUOX-dependent microbe-eliminating capacity and normal host survival. These results demonstrate that the G alpha q-PLC beta-Ca2+_ DUOX-ROS signaling pathway acts as a bona fide first line of defense that enables gut epithelia to dynamically control yeast during the Drosophila life cycle.