Department of Biochemistry, University of Oxford, Oxford, UK.
J Cell Sci. 2009 Dec 15;122(Pt 24):4505-15. doi: 10.1242/jcs.049155. Epub 2009 Nov 24.
In Drosophila, the humoral response characterised by the synthesis of antimicrobial peptides (AMPs) in the fat body (the equivalent of the mammalian liver) and the cellular response mediated by haemocytes (blood cells) engaged in phagocytosis represent two major reactions that counter pathogens. Although considerable analysis has permitted the elucidation of mechanisms pertaining to the two responses individually, the mechanism of their coordination has been unclear. To characterise the signals with which infection might be communicated between blood cells and fat body, we ablated circulating haemocytes and defined the parameters of AMP gene activation in larvae. We found that targeted ablation of blood cells influenced the levels of AMP gene expression in the fat body following both septic injury and oral infection. Expression of the AMP gene drosomycin (a Toll target) was blocked when expression of the Toll ligand Spätzle was knocked down in haemocytes. These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.
在果蝇中,体液反应的特征是脂肪体(相当于哺乳动物的肝脏)中合成抗菌肽 (AMPs),以及血血细胞(吞噬细胞)介导的细胞反应,这两种反应是对抗病原体的主要反应。尽管大量的分析已经阐明了这两种反应各自的机制,但它们的协调机制尚不清楚。为了描述感染可能在血细胞和脂肪体之间传递的信号,我们去除了循环血细胞,并确定了幼虫中 AMP 基因激活的参数。我们发现,靶向去除血细胞会影响败血症损伤和口服感染后脂肪体中 AMP 基因表达的水平。当血血细胞中的 Toll 配体 Spätzle 的表达被敲低时, AMP 基因 drosomycin(一种 Toll 靶标)的表达被阻断。这些结果表明,在幼虫中,两种反应在全身性反应中的整合依赖于细胞因子(spz)的产生,这一过程与哺乳动物的免疫反应非常相似。