> Pathogénie microbienne moléculaire - INSERM U389
• Saga Shigella
• Objectives
• Genetics
• Cell Biology
• Inflammation
• Immunology
• Vaccines
SUMMARY
Scientists in the « Unité de Pathogénie Microbienne Moléculaire » are involved in studying the molecular, cellular and tissular basis of the rupture, invasion and inflammatory destruction of the intestinal barrier by invasive bacteria, as well as the innate and specific defense mechanisms that protect against these infections. Our major model is the bacterium Shigella, a gram-negative bacillus responsible for bacillary dysentery, an acute recto-colitis that causes about 160 million cases every year, with 600,000 to 1 million deaths, mostly young children in the developing areas of the world. For this study, we apply a multidisciplinary approach that encompasses molecular genetics, functional genomics, cell biology, experimental medicine and immunology. The regulatory mechanisms that control expression of bacterial virulence genes are investigated. Their products (i.e. effectors of pathogenicity) modify the behaviour of both epithelial cells and phagocytic cells interacting with their cellular targets. These molecular cross talks between bacteria and cells lead to bacterial internalisation, intracellular motility and cell to cell spread of bacteria. Interaction of invasive shigellae with phagocytic or epithelial cells elicits a cascade of pro-inflammatory signals that causes disruption of the epithelial barrier and, eventually, its destruction. We are also studying the nature of the immune protection against Shigella and how the innate immune response, dominated by strong inflammation, influences the quality of the adaptive immune response. These studies are applied to the development of vaccine candidates against bacillary dysentery. Phase 1 and 2 clinical studies are currently underway.