The first description of Toll-like receptors involved in the response to infection was performed in "Drosophila". culminating in a Nobel prize in 2011. The "Toll" pathway in "Drosophila" is homologous to "Toll-like" pathways in mammals. This regulatory cascade is initiated following pathogen recognition by pattern recognition receptors, particularly of Gram-positive bacteria, parasites, and fungal infection. This activation leads to serine protease signalling cascades ultimately activating the cytokine Spätzle. Alternatively, microbial proteases can directly cleave serine proteases like Persephone that then propagate signalling. The cytokine Spatzle then acts as the ligand for the "Toll" pathway in flies. Upon infection, pro-Spatzle is cleaved by the protease SPE (Spatzle processing enzyme) to become active Spatzle, which binds to the "Toll" receptor located on the cell surface of the fat body and dimerizes for activation of downstream NF-κB signaling pathways, including multiple death domain containing proteins and negative regulators such as the ankyrin repeat protein Cactus. The pathway culminates with the translocation of the NF-κB transcription factors Dorsal and Dif (Dorsal-related immunity factor) into the nucleus.