Signaling pathways implicated in the cellular innate immune responses of Drosophila

The phylogenetically conserved innate immune systems of insects and other invertebrates employ blood cells (hemocytes) that are functionally reminiscent of vertebrate macrophages, attesting to the importance of phagocytosis and other cell-mediated responses in eliminating various pathogens. Receptorligand binding activates signaling cascades that promote collaborative cellular interactions and the production of pathogen-specific cytotoxic responses. Numerous comparative genetic and molecular studies have shown the cytotoxic effector responses made by cells of the innate immune system to be evolutionarily conserved. Comparative analyses of genomic sequences provide convincing evidence that many of the biochemical processes manifested by immune-activated hemocytes are similar to those made by activated vertebrate macrophages. Included in this genomic repertoire are enzymes associated with reactive intermediates of oxygen and nitrogen, cellular redox homeostasis, and apoptosis, the synthesis of extracellular matrix, cell adhesion and pattern recognition molecules. Surprisingly, little is known of the types of cytotoxic molecules produced by invertebrate hemocytes, and the signaling and transcriptional events associated with their collaborative interactions when engaging pathogens and parasites. This review examines certain aspects of the blood cell-mediated defense responses of Drosophila, and some of the signaling pathways that have been implicated in hemocyte activation, differentiation, and the regulation of hematopoiesis.