Bettencourt Raul, Asha H, Dearolf Charles, Ip Y Tony
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
J Cell Biochem. 2004 Jul 1;92(4):849-63. doi: 10.1002/jcb.20123.
Insects possess an antimicrobial defense response that is similar to the mammalian innate immune response. The innate immune system is designed to recognize conserved components of microorganisms called pathogen-associated molecular patterns (PAMPs). How host receptors detect PAMPs and transmit the signals to mount the immune response is being elucidated. Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, have both hemolymph-dependent and -independent responses. Microbial preparations such as lipoteichoic acid (LTA) and peptidoglycan (PGN) can stimulate some responses from dissected and rinsed larval fat bodies. Therefore, at least some aspects of recognition can occur on fat body cell surfaces, bypassing the requirement of hemolymph. Our results also show that supernatants from bacterial cultures can stimulate the nuclear translocation of Dorsal in dissected fat bodies, but this stimulation is strictly hemolymph-dependent. Various biochemical assays suggest that the factors from bacterial supernatants that stimulate the hemolymph-dependent nuclear translocation are likely made up of proteins. We further show that Dorsal mutant larvae have much lower phenoloxidase activity, consistent with a more important role of Dorsal in innate immunity than previously shown.
昆虫拥有一种类似于哺乳动物先天免疫反应的抗菌防御反应。先天免疫系统旨在识别被称为病原体相关分子模式（PAMPs）的微生物保守成分。宿主受体如何检测PAMPs并传递信号以引发免疫反应正在被阐明。通过在体外试验中使用绿色荧光蛋白标记的背侧蛋白（GFP-Dorsal）、分化因子（Dif）和 relish 蛋白，我们证明果蝇脂肪体作为主要的免疫组织，具有依赖血淋巴和不依赖血淋巴的反应。微生物制剂如脂磷壁酸（LTA）和肽聚糖（PGN）可以刺激解剖并冲洗后的幼虫脂肪体产生一些反应。因此，至少某些识别过程可以在脂肪体细胞表面发生，而无需血淋巴参与。我们的结果还表明，细菌培养物的上清液可以刺激解剖后的脂肪体中背侧蛋白的核转位，但这种刺激严格依赖血淋巴。各种生化分析表明，刺激依赖血淋巴的核转位的细菌上清液中的因子可能由蛋白质组成。我们进一步表明，背侧蛋白突变体幼虫的酚氧化酶活性要低得多，这表明背侧蛋白在先天免疫中的作用比以前所显示的更为重要。
