Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila

• Published in: Microbes and infection Vol. 5; no. 10; pp. 815 - 824
• Main Authors: Pearson, Alan M., Baksa, Katalin, Rämet, Mika, Protas, Meredith, McKee, Mary, Brown, Dennis, Ezekowitz, R.Alan B.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.08.2003; Amsterdam Elsevier; Paris
• Subjects: Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Animals; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Contractile Proteins; Cytochalasin D - pharmacology; Cytoskeleton; D-SCAR protein; D-WASp protein; Down-Regulation; Drosophila; Drosophila - immunology; Drosophila - physiology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Escherichia coli; Fundamental and applied biological sciences. Psychology; Hemocytes - cytology; Hemocytes - metabolism; Hemocytes - physiology; Hemocytes - ultrastructure; Innate immunity; Invertebrates; Microfilament Proteins - genetics; Microfilament Proteins - physiology; Mutagenesis, Insertional; Mutation; Nemathelminthia. Plathelmintha; Phagocytosis; Phagocytosis - drug effects; Phagocytosis - genetics; Phagocytosis - physiology; Physiology. Development; profilin; Profilins; Staphylococcus aureus; Up-Regulation; Wiskott-Aldrich Syndrome Protein; Cytoskeleton; Innate immunity; Drosophila; Phagocytosis; Regulation(control); Arthropoda; Insecta; Natural immunity; Invertebrata; Diptera; Drosophilidae
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/S1286-4579(03)00157-6

Phagocytosis is a complex and apparently evolutionarily conserved process that plays a central role in the immune response to infection. By ultrastructural and functional criteria, Drosophila hemocyte (macrophage) phagocytosis resembles mammalian phagocytosis. Using a non-saturated forward genetic screen for larval hemocyte phagocytosis mutants, D-SCAR and profilin were identified as important regulators of phagocytosis in Drosophila. In both hemocytes ex vivo and the macrophage-like S2 cell line, lack of D-SCAR significantly decreased phagocytosis of Escherichia coli and Staphylococcus aureus. In contrast, profilin mutant hemocytes exhibited increased phagocytic activity. Analysis of double mutants suggests that D-SCAR and profilin interact during phagocytosis. Finally, RNA interference studies in S2 cells indicated that the D-SCAR homolog D-WASp also participates in phagocytosis. This study demonstrates that Drosophila provides a viable model system in which to dissect the complex interactions that regulate phagocytosis.