title: TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis.
abstract: Nonaspanins are characterised by a large N-terminal extracellular domain and nine putative transmembrane domains. This evolutionarily conserved family comprises three members in Dictyostelium discoideum (Phg1A, Phg1B and Phg1C) and Drosophila melanogaster, and four in mammals (TM9SF1-TM9SF4), the function of which is essentially unknown. Genetic studies in Dictyostelium demonstrated that Phg1A is required for cell adhesion and phagocytosis. We created Phg1A/TM9SF4-null mutant flies and showed that they were sensitive to pathogenic Gram-negative, but not Gram-positive, bacteria. This increased sensitivity was not due to impaired Toll or Imd signalling, but rather to a defective cellular immune response. TM9SF4-null larval macrophages phagocytosed Gram-negative E. coli inefficiently, although Gram-positive S. aureus were phagocytosed normally. Mutant larvae also had a decreased wasp egg encapsulation rate, a process requiring haemocyte-dependent adhesion to parasitoids. Defective cellular immunity was coupled to morphological and adhesion defects in mutant larval haemocytes, which had an abnormal actin cytoskeleton. TM9SF4, and its closest paralogue TM9SF2, were both required for bacterial internalisation in S2 cells, where they displayed partial redundancy. Our study highlights the contribution of phagocytes to host defence in an organism possessing a complex innate immune response and suggests an evolutionarily conserved function of TM9SF4 in eukaryotic phagocytes.
authors.affiliation: CEA, iRTSV, LTS, 38054 Grenoble, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bergeret
authors.forename: Jackie
authors.initials: J
authors.lastname: Perrin
authors.forename: Michael
authors.initials: M
authors.lastname: Williams
authors.forename: Didier
authors.initials: D
authors.lastname: Grunwald
authors.forename: Elodie
authors.initials: E
authors.lastname: Engel
authors.forename: Dominique
authors.initials: D
authors.lastname: Thevenon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Taillebourg
authors.forename: Franz
authors.initials: F
authors.lastname: Bruckert
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004023:Dictyostelium / Q000235:genetics / Q000276:immunology; D004331:Drosophila melanogaster; D004926:Escherichia coli / Q000276:immunology*; D006434:Hemocytes / Q000166:cytology / Q000276:immunology*; D007113:Immunity, Innate / Q000502:physiology*; D007814:Larva / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008322:Mammals / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000235:genetics / Q000276:immunology; D010586:Phagocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D008565:Membrane Proteins