Danger signal and PAMP sensing define binary signaling pathways upstream of Toll

In drosophila, fungal and Gram-positive bacterial molecular determinants are detected by circulating pattern recognition receptors (PRRs). Previous findings suggest that these PRRs activate yet unidentified serine protease cascades culminating in the cleavage of Spaetzle, the endogenous Toll receptor ligand, and triggering the immune response. We demonstrate here that the Grass protease defines a common activation cascade for PRR-mediated fungal and Gram-positive bacterial detection. The serine protease Persephone, previously shown to be specific for fungal detection in a cascade activated by secreted fungal proteases, was also required for sensing of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a parallel proteolytic cascade activated by danger signals such as abnormal proteolytic activities.