Negative regulation of immune responses on the fly

NF-kappa B-dependent immune responses are tightly controlled so as to avoid runaway inflammation. One easy model to study the negative regulation of these pathways is provided by the Drosophila melanogaster immune deficiency (IMD) pathway, which regulates both systemic and epithelial immune responses against bacteria. Ragab et al (2011) report in this issue of the EMBO Journal that the Ras/MAPK pathway negatively regulates the IMD pathway when activated by the PDGF/VEGF receptor (PVR), a process mediated by the PIRK/Rudra/PIMS inhibitor. This study raises interesting questions regarding the biological significance of IMD negative regulation in diverse settings.