Leulier F, Rodriguez A, Khush R S, Abrams J M, Lemaitre B
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, France.
EMBO Rep. 2000 Oct;1(4):353-8. doi: 10.1093/embo-reports/kvd073.
The Drosophila innate immune system discriminates between pathogens and responds by inducing the expression of specific antimicrobial peptide-encoding genes through distinct signaling cascades. Fungal infection activates NF-kappaB-like transcription factors via the Toll pathway, which also regulates innate immune responses in mammals. The pathways that mediate antibacterial defenses, however, are less defined. We have isolated loss-of-function mutations in the caspase encoding gene dredd, which block the expression of all genes that code for peptides with antibacterial activity. These mutations also render flies highly susceptible to infection by gram-negative bacteria. Our results demonstrate that Dredd regulates antibacterial peptide gene expression, and we propose that Dredd, Immune Deficiency and the P105-like rel protein Relish define a pathway that is required to resist gram-negative bacterial infections.
果蝇的先天免疫系统能够区分病原体，并通过不同的信号级联反应诱导特定抗菌肽编码基因的表达来做出反应。真菌感染通过Toll途径激活类NF-κB转录因子，该途径也调节哺乳动物的先天免疫反应。然而，介导抗菌防御的途径尚不清楚。我们在编码半胱天冬酶的基因dredd中分离到功能缺失突变，这些突变阻断了所有编码具有抗菌活性肽的基因的表达。这些突变还使果蝇对革兰氏阴性菌感染高度敏感。我们的结果表明，Dredd调节抗菌肽基因的表达，并且我们提出Dredd、免疫缺陷和P105样rel蛋白Relish定义了一条抵抗革兰氏阴性菌感染所需的途径。
