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Scientific article
Open access
English

TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis

Published inJournal of cell science, vol. 121, no. Pt 20, p. 3325-3334
Publication date2008
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.

Keywords
  • Animals
  • Cell Adhesion/genetics/immunology
  • Cell Line
  • Dictyostelium/genetics/immunology
  • Drosophila melanogaster
  • Escherichia coli/immunology
  • Hemocytes/cytology/immunology
  • Immunity, Innate/physiology
  • Larva/genetics/immunology/microbiology
  • Mammals/genetics/immunology
  • Membrane Proteins/genetics/immunology
  • Mutation/genetics/immunology
  • Phagocytes/cytology/immunology
  • Phagocytosis/genetics/immunology
  • Signal Transduction/genetics/immunology
  • Staphylococcus aureus/immunology
Research group
Citation (ISO format)
BERGERET, Evelyne et al. TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. In: Journal of cell science, 2008, vol. 121, n° Pt 20, p. 3325–3334. doi: 10.1242/jcs.030163
Main files (1)
Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal0021-9533
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225downloads

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