Journal Article

Phagocytosis and comparative innate immunity: learning on the fly

Ezekowitz, R. Alan, Stuart, Lynda M.

2008

Overview

Key Points Phagocytosis, the internalization of particles by cells, is involved in development, tissue homeostasis and host defence. Aspects of this process are highly conserved between species and hence studies in model organisms, such as Drosophila melanogaster , have been informative. Particle internalization is not simply a mechanism of waste disposal but rather essential for the formation of the phagosome, the organelle that is generated around the internalized particle. As in mammals, D. melanogaster phagosomes are highly complex compartments and are central to many of the effector functions of phagocytes. Phagocytosis is triggered after ligation of cell-surface receptors. Similar to mammals, D. melanogaster uses multiple mechanisms of bacterial recognition, such as complement-like opsonization and scavenger receptors. In addition, studies in D. melanogaster have highlighted a new family of phagocytic receptors that use epidermal growth factor (EGF)-like repeats to bind ligands. Fruit flies have an alternative to the highly variable antibodies found in mammals and instead use DSCAM (Down syndrome cell-adhesion molecule), an immunoglobulin-superfamily member that shows remarkable variability, that may act as both an opsonin and a cell-surface receptor. RNA-interference-based screens have shown that much of the machinery downstream of the cell-surface receptors are common between flies and humans. Studies in D. melanogaster have also suggested roles for the coatamer protein complex and the exocyst complex in the process of phagocytosis. In addition, studies in D. melanogaster have added to our understanding of the role of phagocytosis in pathogen sensing. Furthermore, D. melanogaster phagocytes may potentially be involved in immune adaptation and the processing of internalized antigens. Studies in Drosophila melanogaster are proving fruitful for our understanding of phagocytosis in development, tissue homeostasis and host defence. In this Review, parallels are drawn between phagocytosis in flies and mammals, providing insight into its complexity and the evolutionary origins of immunity. Phagocytosis, the engulfment of material by cells, is a highly conserved process that arose before the development of multicellularity. Phagocytes have a key role in embryogenesis and also guard the portals of potential pathogen entry. They discriminate between diverse particles through the array of receptors expressed on their surface. In higher species, arguably the most sophisticated function of phagocytes is the processing and presentation of antigens derived from internalized material to stimulate lymphocytes and long-lived specific immunity. Central to these processes is the generation of a phagosome, the organelle that forms around internalized material. As we discuss in this Review, over the past two decades important insights into phagocytosis have been gleaned from studies in the model organism Drosophila melanogaster .

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biology / Biomedical and Life Sciences / Biomedicine / Cells / Drosophila melanogaster / Drosophila melanogaster - immunology / Embryonic development / Embryonic growth stage / Genetic aspects / Health aspects / Immunity, Innate / Immunology / Insects / Lymphocytes / Microorganisms / Natural immunity / Pathogens / Phagocytosis / review-article