Phagocytic receptors and opsonins in Drosophila
Christine Kocks,
Laboratory of Developmental Immunology, Massachusetts General Hospital
The fruit fly Drosophila melanogaster has an effective innate pathogen defense system. Our laboratory uses Drosophila as a model to study basic mechanisms of phagocytosis, in particular how fly phagocytes recognize and engulf bacteria. Recently, we identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila (Kocks et al 2005 Cell 123). Our findings illustrate the importance of phagocytosis in the Drosophila host defense against bacterial pathogens, and suggest that Eater is a major phagocytic receptor.
The predicted extracellular domain of Eater consists mostly of EGF-like repeats. The four N-terminal of these mediate binding to a broad range of microbes, and can be inhibited with polyanionic ligands. This binding behavior is reminiscent of mammalian scavenger receptors, a large group of structurally non-related molecules implicated in the endocytosis of altered self ligands and in host defense. Secreted and membrane-bound proteins harboring multiple EGF-like repeats homologous to Eater occur in Drosophila, other insects and in nematodes, suggesting that Eater may be a prototype of a new family of pattern recognition molecules used in the animal kingdom.
In addition to discussing the Eater receptor and EGF-like repeats as an emerging new paradigm for pattern recognition, I will give an overview of other phagocytic receptors and opsonins in Drosophila.