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First published online 16 September 2008
doi: 10.1242/jcs.030163

Journal of Cell Science 121, 3325-3334 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Evelyne Bergeret1,2,3, Jackie Perrin1,2,3, Michael Williams4, Didier Grunwald1,2,3, Elodie Engel1,2,3, Dominique Thevenon1,2,3, Emmanuel Taillebourg1,2,3, Franz Bruckert5, Pierre Cosson6 and Marie-Odile Fauvarque1,2,3,*

1 CEA, iRTSV, LTS, 38054 Grenoble, France
2 INSERM U873, 38054 Grenoble, France
3 Université Joseph Fourier, 38000 Grenoble, France
4 Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK
5 Minatec, Grenoble Institute of Technology, LMPG, 38054 Grenoble, France
6 Centre Médical Universitaire, Département de Physiologie Cellulaire et Métabolisme, Université de Genève, CH-1211 Geneva 4, Switzerland

* Author for correspondence (e-mail: marie-odile.fauvarque{at}cea.fr)

Accepted 7 July 2008

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.

Key words: Innate immunity, Macrophages, Adhesion, Phagocytosis, Cytoskeleton, Nonaspanin


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Getting defensive with nonaspanins

JCS 2008 121: 2001. [Full Text]  





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