title: Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance.
abstract: Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3ζ, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis. Of these identified genes, 14-3-3ζ had an evolutionarily conserved role in phagocytosis: bacterial phagocytosis was compromised when 14-3-3ζ was targeted with RNAi in primary Drosophila hemocytes and when the orthologous genes Ywhab and Ywhaz were silenced in zebrafish and mouse RAW 264.7 cells, respectively. In Drosophila and zebrafish infection models, 14-3-3ζ was required for resistance against Staphylococcus aureus. We conclude that 14-3-3ζ is essential for phagocytosis and microbial resistance in insects and vertebrates.
authors.affiliation: Departments of Pediatrics, Biocenter Oulu, University of Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ulvila
authors.forename: Leena-Maija
authors.initials: LM
authors.lastname: Vanha-aho
authors.forename: Anni
authors.initials: A
authors.lastname: Kleino
authors.forename: Mari
authors.initials: M
authors.lastname: Vähä-Mäkilä
authors.forename: Milka
authors.initials: M
authors.lastname: Vuoksio
authors.forename: Sinikka
authors.initials: S
authors.lastname: Eskelinen
authors.forename: Dan
authors.initials: D
authors.lastname: Hultmark
authors.forename: Christine
authors.initials: C
authors.lastname: Kocks
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
authors.forename: Mataleena
authors.initials: M
authors.lastname: Parikka
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D051339:Actin Depolymerizing Factors / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D005260:Female; D020868:Gene Silencing; D017344:Genes, Insect; D006434:Hemocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000276:immunology / Q000382:microbiology
chemical_list: D048948:14-3-3 Proteins; D051339:Actin Depolymerizing Factors; D034741:RNA, Small Interfering