Eater, a Transmembrane Protein Mediating Phagocytosis of Bacterial Pathogens in Drosophila

Christine Kocks, Ju Hyun Cho, Nadine Nehme, Johanna Ulvila, Alan M. Pearson, Marie Meister, Charles Strom, Stephanie L. Conto, Charles Hetru, Lynda M. Stuart, Thilo Stehle, Jules A. Hoffmann, Jean-Marc Reichhart, Dominique Ferrandon, Mika Ramet and R. Alan B. Ezekowitz

Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
UPR9022 du Centre National de Recherche Scientifique, Institut de Biologie Moleculaire et Cellulaire, 67084 Strasbourg, France
Department of Pediatrics and Biocenter Oulu, University of Oulu, Finland
Institute of Medical Technology, University of Tampere, Finland
Department of Pediatrics, Tampere University Hospital, Finland

Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.