Host-pathogen interactions in Drosophila

The fly has a multilayered immune system consisting of at least seven defensive mechanisms that might be encountered by a pathogen as it tries to enter the body of the fly. Moving from the outside of the body to the inside these are: (1) regulation of the native microbiota in the gut through antimicrobial peptides (AMPs) and reactive oxygen species; (2) the barrier epithelial response, which can recognize infections and wounds, produce local AMPs and send signals to the rest of the body; (3) the clotting response, which not only seals wounds and prevents bleeding, but can physically trap bacteria; (4) the phenoloxidase response, which deposits melanin at the site of an immune reaction, releasing potentially antimicrobial reactive oxygen species; (5) the phagocytic response, through which phagocytes can kill microbes directly by either encapsulation or phagocytosis, or indirectly by releasing systemic signals; (6) the systemic AMP response, which involves the release of massive quantities of AMPs from the fat body (the liver analog) into the circulation; and (7) the RNAi response, which is required to fight viral infections. The majority of the work in flies concentrates on the immune response in the fat body. The transcriptional response of the fat body is so large that 1000-fold inductions can be measured even when whole fly homogenates are assayed. This transcriptional response is primarily under the control of three Rel-related transcription factors, Dif, Dorsal and Relish; these transcription factors are themselves regulated by two cross-reacting pathways, Toll and immune deficiency (Imd).