The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.
The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.
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DAF-16/FOXO 转录因子充当表皮先天免疫的调节剂。
DOI：
10.1371/journal.ppat.1003660
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Zhang KQ
中科院分区：
文献类型：
--
作者：
Zou CG;Tu Q;Niu J;Ji XL;Zhang KQ
秀丽隐杆线虫DAF-16转录因子对多种生物过程，特别是寿命和抗逆性至关重要。破坏DAF-2信号级联可促进DAF-16的激活，并使其抵抗病原菌的杀伤，如铜绿假单胞菌、金黄色葡萄球菌和粪肠球菌。然而，daf-16突变体对这些细菌表现出与野生型动物相似的敏感性，这表明daf-16通常不会被这些细菌病原体激活。在本报告中，我们证明了DAF-16可以在野生型动物的真菌感染和损伤中直接激活，而不依赖于DAF-2途径。真菌感染和损伤启动Gαq信号级联，导致Ca2+释放。Ca2+介导双氧化酶BLI-3的激活，导致活性氧（ROS）的产生。然后ROS通过ste20样激酶-1/CST-1激活DAF-16。我们的研究结果表明，表皮中的DAF-16是真菌感染和损伤后存活所必需的。因此，EGL-30-Ca2+-BLI-3-CST-1-DAF-16信号代表了一个以前未知的调节表皮损伤反应的途径。在自然环境中，动物会遇到不同的病原体。因此，为了生存，生物体内的不同组织必须发展出特定的免疫系统。表皮作为一种物理屏障，是各种动物抵御感染和身体伤害的第一道防线。天然噬线虫真菌，如coniospora Drechmeria和Clonostachys rosea，通过产生分生孢子感染秀丽隐杆线虫的表皮。本研究表明，表皮中的DAF-16/FOXO转录因子在秀丽隐杆线虫抵抗真菌感染和物理损伤中具有直接作用。我们发现EGL-30/EGL-8/IP3/ITR-1信号通路在真菌感染后通过IP3及其受体ITR-1触发表皮Ca2+释放。Ca2+释放通过激活双氧化酶BLI-3诱导活性氧（ROS）的产生。ROS反过来以ste20样激酶-1/ cst -1依赖的方式介导DAF-16的激活。因此，DAF-16可以在表皮中以细胞自主的方式作为真菌感染和物理损伤的免疫反应的主动调节剂。
The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca2+ release. Ca2+ mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS). ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca2+-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response. In the natural environment, animals encounter different pathogens. Thus, different tissues within an organism must develop specific immune systems for survival. The epidermis acts as a physical barrier and represents a first line of defense against infection and physical injury in a variety of animals. Natural nematophagous fungi, such as Drechmeria coniospora and Clonostachys rosea, infect the epidermis of the roundworm Caenorhabditis elegans by producing conidia. Here we demonstrated that the DAF-16/FOXO transcription factor in the epidermis has a direct role in C. elegans defense against fungal infection and physical injury. We found that the EGL-30/EGL-8/IP3/ITR-1 signaling pathway triggers epidermal Ca2+ release through IP3 and its receptor ITR-1 after fungal infection. Ca2+ release induces the production of reactive oxygen species (ROS) by activating a dual-oxidase BLI-3. ROS in turn mediate DAF-16 activation in a Ste20-like kinase-1/CST-1-dependent manner. Thus, DAF-16 could act in a cell-autonomous way in the epidermis as an active regulator of immune responses to fungal infection and physical injury.
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影响因子：
30.3
作者：
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