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

E Bergeret, J Perrin, Michael Jon Williams, Grunwald D, D Thevenon, E Taillebourg, F Bruckert, P Cosson , MO Fauvarque (Corresponding Author)

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3325-3334
Number of pages10
JournalJournal of Cell Science
Volume121
Issue number20
Early online date16 Sep 2008
DOIs
Publication statusPublished - 15 Oct 2008

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Cytophagocytosis
Hemocytes
Dictyostelium
Phagocytes
Phagocytosis
Cell Adhesion
Cellular Immunity
Drosophila
Wasps
Gram-Positive Bacteria
Drosophila melanogaster
Actin Cytoskeleton
Innate Immunity
Diptera
Ovum
Larva
Mammals
Macrophages
Escherichia coli

Cite this

Bergeret, E., Perrin, J., Williams, M. J., D, G., Thevenon, D., Taillebourg, E., ... Fauvarque, MO. (2008). TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. Journal of Cell Science, 121(20), 3325-3334. https://doi.org/10.1242/jcs.030163

TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. / Bergeret, E; Perrin, J; Williams, Michael Jon; D, Grunwald; Thevenon, D; Taillebourg, E; Bruckert, F; Cosson , P; Fauvarque, MO (Corresponding Author).

In: Journal of Cell Science, Vol. 121, No. 20, 15.10.2008, p. 3325-3334.

Research output: Contribution to journalArticle

Bergeret, E, Perrin, J, Williams, MJ, D, G, Thevenon, D, Taillebourg, E, Bruckert, F, Cosson , P & Fauvarque, MO 2008, 'TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis', Journal of Cell Science, vol. 121, no. 20, pp. 3325-3334. https://doi.org/10.1242/jcs.030163
Bergeret E, Perrin J, Williams MJ, D G, Thevenon D, Taillebourg E et al. TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. Journal of Cell Science. 2008 Oct 15;121(20):3325-3334. https://doi.org/10.1242/jcs.030163
Bergeret, E ; Perrin, J ; Williams, Michael Jon ; D, Grunwald ; Thevenon, D ; Taillebourg, E ; Bruckert, F ; Cosson , P ; Fauvarque, MO. / TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis. In: Journal of Cell Science. 2008 ; Vol. 121, No. 20. pp. 3325-3334.
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