Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Immune Regulation and Vaccinology Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
The activity is focused on the understanding of the mechanisms that control the activation and regulation of T cell responses and on the development of new strategies of vaccination against tumors and infections. This includes: Development of anti-cancer vaccines - Analysis of immunosuppresion within tumor - Analysis of T cell responses induced by DC - Anti-mycobacterial immunity. There is also a special focus on Immune regulation and vaccine science in neonates. Understanding the innate and adaptive regulatory mechanisms responsible for the high susceptibility to infections in newborns to improve vaccine design. Study of crosstalk between neonatal Bregs and DC, in controlling pro-inflammatory and Th1 responses. Recent identification of the regulatory role of neutrophils in bacterial infection following co-activation of TLR and C-type lectins. We are currently investigating, both in mice and humans, innate activation pathways that activate neonatal DC and bypass regulatory mechanisms.
Contribution to the programme
Irrespective of host genetic factors, extremes of age are characterized by a higher susceptibility to particular infections. This remains ill understood due to gaps in the knowledge of the immune system of the newborn and the elderly. Thus, these populations constitute privileged targets and reservoirs for emerging diseases. Challenging the traditional view, we recently evidenced immunological unfitness related to age-specific regulatory mechanisms through negative tuning of neonatal immune responses. We aim at defining the immunological signatures of age-dependent susceptibility to infections at the molecular and cellular levels. We established a Mouse-Human experimental platform to study pathogen-neonatal immune host interactions. Ultimately, linking immune cell specific gene expression, phenotypes and functions will establish an age-related functional map of susceptibility and immunity in infections for which early and late life populations are at risk.
References over the past 5 years
2. Zhang, X., L. Majlessi, E. Deriaud, C. Leclerc, and R. Lo-Man. 2009. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity 31:761-771.
3. Zhang, X., E. Deriaud, X. Jiao, D. Braun, C. Leclerc, and R. Lo-Man. 2007. Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells. J Exp Med 204:1107-1118.
4. S. Bay, S. Fort, L. Birikaki, C. Ganneau, E. Samain, Y-M. Coïc, F. Bonhomme, E. Dériaud, C. Leclerc, R. Lo-Man. 2009. Induction of a melanoma-specific antibody response by a monovalent, but not a divalent, synthetic GM2 neoglycopeptide. ChemMedChem 4:582Leclerc, C., C. Brose, C. Nouze, F. Leonard, L. Majlessi, S. Becker, H. von Briesen, and R. Lo-Man. 2008. Immobilized cytokines as biomaterials for manufacturing immune cell based vaccines. J Biomed Mater Res A 86:1033