eLife:浙大农学院叶恭银教授团队揭示5-羟色胺调控昆虫先天免疫

2016年3月14日，国际知名期刊《eLife》在线发表了浙江大学农学院昆虫科学研究所叶恭银教授团队的一篇研究成果，叶恭银教授团队首次发现了5-羟色胺可以通过5-羟色胺受体5-HT1B和5-HT2B调控昆虫血细胞吞噬。生物胺如5-羟色胺、多巴胺和章鱼胺等是昆虫体内一类非常重要的神经小分子，广泛调控昆虫的各种生理功能和行为。它们在昆虫体内通过对应的g蛋白偶联受体发挥作用，这些受体也是杀虫剂开发的潜在靶标。博士生齐易香和黄佳副教授为论文共同第一作者，通讯作者为黄佳副教授和叶恭银教授。

该研究发现鳞翅目害虫菜青虫的血细胞能够自身合成和分泌5-羟色胺，用药理学或RNAi干扰其合成酶的功能会显著降低血细胞吞噬细菌的能力。菜青虫血细胞主要表达5-HT1B和5-HT2B受体，用拮抗剂阻断或者RNAi干扰这两个受体的功能也会显著影响血细胞的吞噬能力。通过对模式生物黑腹果蝇5-羟色胺受体的敲除突变体和血细胞特异性RNAi的实验，进一步在遗传学上证实了在5-羟色胺受体缺失或表达下调的情况下，果蝇由于血细胞吞噬能力的降低从而在被病原菌感染后更加容易死亡。该研究在分子水平上证实昆虫也与哺乳动物一样可以通过5-羟色胺来调控神经系统和免疫系统的相互作用，并第一次在遗传学上发现昆虫利用血细胞上的神经小分子信号通路来帮助自身对抗病原微生物，提示了通过药物特异性地干扰昆虫免疫系统从而增强生物杀虫剂效力的可能性，对开辟害虫防治新途径有重要的理论指导意义。

原文链接：

Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors

原文摘要：

Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogastermutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

DOI: http://dx.doi.org/10.7554/eLife.12241

作者：叶恭银