Etude de l'intéraction entre inflammation et infection chez la drosophile

Interaction between inflammation and infection in Drosophila melanogaster

• Auteur / Autrice : Ramy Ragheb
• Direction : Catherine Nguyen, Laurence Röder
• Type : Thèse de doctorat
• Discipline(s) : Biologie
• Date : Soutenance le 15/12/2016
• Etablissement(s) : Aix-Marseille
• Ecole(s) doctorale(s) : Ecole Doctorale Sciences de la Vie et de la Santé (Marseille)
• Partenaire(s) de recherche : Laboratoire : TAGC. Technological advances for genomics and clinics (marseille)
• Jury : Président / Présidente : Julien Royet
• Jury : Examinateurs / Examinatrices : Jean-Marc Cavaillon
• Jury : Rapporteurs / Rapporteuses : Armel Gallet, Marie-Odile Fauvarque

Mots clés

Mots clés contrôlés

Drosophiles

Sepsis

Inflammation

Infections

Immunité

Mots clés libres

Immunité

Infection

Inflammation

Sepsis

Drosophile

Immunity

Infection

Inflammation

Sepsis

Drosophila

Résumé

.

In mammals, both sterile wounding and infection induce inflammation and activate the innate immune system, and combining both challenges can lead to severe health defects, revealing that the balance between the intensity and resolution of the inflammatory response is central for the organism's fitness. The underlying mechanisms remain however elusive. Using Drosophila as a model, we show that a sterile wounding induces a reduced resistance to a bacterial challenge and is accompanied by an increased host mortality upon infection. We further investigate the underlying molecular mechanisms of flies susceptibility to bacterial infection by comparing the transcriptome landscape of SH flies (Simple Hit: infection only), DH flies (Double Hit: trauma + infection) and control flies (sterile trauma alone) during the early steps. We observed that genes with increased expression in DH flies compared to SH ones are significantly enriched for stress related annotations, including members of the JNK pathway and demonstrate that the JNK pathway plays a central role in the DH phenotype. In addition, the CrebA/Creb3-like transcription factor and its targets are up regulated in SH flies and we show that CrebA is required for mounting the innate immune response. We also investigated the potential role of the TNF receptor grnd in SH and DH flies. Our results reveal its function in innate immune response since flies with reduced grnd function display reduced viability upon infection. Drosophila thus appears as a relevant model to investigate the complex interactions between inflammation and infection and allows to unravel key pathways involved in the acquisition of a hyper-inflammatory state.