Cel Tuberculosis is a disease in which traditional prophylactic approaches have been largely unsuccessful. The search for new therapeutic interventions is required to overcome the low compliance to complex chemo-antibiotic regimens and to avoid multi-drug resistance. Aim of this project is to produce new knowledge and insight that bear a potential for new therapeutic or prophylactic interventions focusing on one of the most critical immune evasion mechanism of Mycobacterium tuberculosis (Mtb): the capacity to switch to a dormant status of latency, which causes its persistence in the host. The switch implies a reduction/abrogation of the synthesis of antigens required for activation of T lymphocytes primed in the early phase of infection, while new products are generated with possible antigenic properties. MILD-TB will analyse the variations in lipid metabolism and composition associated to dormancy. The immune response against mycobacterial lipid antigens represents an important mechanism of defense. However, no data are available on the antigenicity of lipids produced by dormant Mtb. MILD-TB will analyse the immunogenicity of lipids isolated from non replicating Mtb produced in vitro using a culture method resembling Mtb dormancy in vivo. Lipids will be analysed in reference strains and clinical isolates from endemic areas and will be compared with those produced by replicating Mtb. The immunogenicity of lipids specifically isolated from dormant Mtb will be determined using pre-existing and newly established lipid-specific T cell clones and by immunizing CD1b transgenic mice. Parallel analysis of susceptibility of dormant Mtb to T-dependent mechanisms of direct or indirect killing will be performed to explore the possibility of new therapeutic or prophylactic interventions based on vaccination with lipid-antigens or on immune-modulation. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistance Program(-y) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Temat(-y) LSH-2005-2.3.0-4 - New approaches for research into host/vector-pathogen interaction for HIV/AIDS, malaria and tuberculosis LIFESCIHEALTH - Life sciences, genomics and biotechnology for health Zaproszenie do składania wniosków FP6-2005-LIFESCIHEALTH-6 Zobacz inne projekty w ramach tego zaproszenia System finansowania STREP - Specific Targeted Research Project Koordynator ISTITUTO SUPERIORE DI SANITÀ Wkład UE Brak danych Adres Viale Regina Elena 299 ROMA Włochy Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITÄT BASEL Szwajcaria Wkład UE Brak danych Adres Petersgraben 35 BASEL Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE Francja Wkład UE Brak danych Adres 16, Avenue Edouard Belin 24367 TOULOUSE Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych ISTITUT PASTEUR DE COTE D'IVOIRE' Wybrzeże Kości Słoniowej Wkład UE Brak danych Adres Abidjan 07 07BP500 ABIDJAN Zobacz na mapie Koszt całkowity Brak danych