To ensure host survival, virus-infected cells are targeted for elimination by host immune mechanisms. While vertebrates successfully accommodate such task to their sophisticated immune system, the mechanism how invertebrates, being equipped with a simple innate immunity, accomplish this vital responsibility remains unknown. Our laboratory previously reported that influenza virus-infected cells are engulfed by macrophages in an apoptosis-dependent manner resulting in the inhibition of virus growth in mice. Owing to the similarity of phagocyte???s characteristics and functions between mammals and Drosophila, I anticipated that a similar response is also employed in insects as a part of innate immunity. To assess this, I established infection model system using Drosophila C virus (DCV). Infection of Drosophila S2, an embryonic cell-derived cell line, was characterized by massive production of progenitor virus accompanied by an elevated level of cells undergoing apoptosis. Such cells were phagocytosed by l(2)mbn, a larval phagocyte-derived cell line, in a manner inhibitable by either a caspase inhibitor, phosphatidylserine-containing liposomes, or by RNAi knockdown of engulfment receptors in phagocytes. Furthermore, the pathogenic effect of DCV in vivo was increased, when flies were pre-treated with latex beads to inhibit phagocytosis, depleted of the engulfment receptors, or manipulated to express a phosphatidylserine-binding protein. Taken together, these results suggested that apoptosis-dependent phagocytic removal of virus-infected cells exists as a part of innate immunity and is evolutionarily conserved from flies to mice.
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