Thesis presented June 03, 2009

Abstract:
In eukaryotes, phagocytic cells are involved in the defense against pathogens by insuring the recognition of foreign bodies, their internalization and elimination. We developed the use of the fly Drosophila melanogaster for the prospective study of the phagocytes contribution in the innate immunity and their role in host-pathogen interactions.
In phagocytes, the GTPases of the family Rho have an essential role in the actin cytoskeleton dynamics that take place during cellular adhesion and pathogen internalisation. We proved that the RhoGTPase Rac2 is specifically involved in drosophila cellular immune response and contributes to the resistance in infections by the pathogenic bacteria Pseudomonas aeruginosa. This bacteria raises major public health problems, in particular at the patients affected by cystic fibrosis. I focused in the toxin ExoS of P. aeruginosa which is injected in host cells targeting​ RhoGTPases. In particular, Rac2 is inhibited by this toxin resulting in reduced phagocytosis and resistance to infection. In parallel, I participated in the identification of new virulence factors of P. aeruginosa in association with Pr P. Cosson (Centre Médical Universitaire, Geneva).
My work also concerned the research for new players of the cellular immune response. I looked into an evolutionary conserved family of proteins, the nonaspanins also called TM9SF proteins, who’s function in the phagocytosis had been previously shown in amoeba. We proved that TM9SF4 plays an important role in drosophila infection resistance via its implication in phagocytosis and cellular adhesion.

Keywords:
Bacterial virulence factors, Innate immune response, RhoGTPases, Phagocytosis, Drosophila melanogaster

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