My major scientific aim has been to try to understand the mechanisms of complex infection processes by integrating complementary approaches such as molecular genetics of prokaryotes, cell biology, experimental medicine and immunology. Our paradigm has been (and still is) the process of rupture, invasion and inflammatory destruction of the intestinal epithelium by the Gram negative enteric pathogen Shigella. We have identified most of the bacterial genes and gene products involved in entry into cells, intracellular motility, cell to cell spread, cell apoptosis and NF-B activation. In parallel, we have tried to constantly integrate these in vitro data into more complex in vivo models of infection in animals, thus putting those approaches in the context of the host innate and specific immune response. We have recently shown that the invasive microorganism was actually able to "play" with components of this response, at the early stage of infection. Thus regulating the innate response to promote its survival and efficient colonization.
Based on this integrative approach we have been able to develop promising live attenuated oral vaccines against Shigella infection which are currently under trial in endemic areas.
Institut Pasteur
Unité de Pathogénie Microbienne Moléculaire
INSERM U389
28 rue du Dr Roux
F - 75724 PARIS Cédex 15
France
E-mail:
| Fellows | Coordinator
