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Molecular markers of M. tuberculosis early interactions with host phagocytes

Objective

Tuberculosis is a major public health problem. One third of the world population is estimated to carry latent infections and the global incidence of TB increases by 2% annually. An additional major problem is the increasing incidence of
multi-drug resistances (MDR) in Eastern Europe. Such a situation will require new types of intervention and a much better follow up on the TB patients. The goal of this project is to develop and design new markers of protection and to identify
unique molecular patterns both in the microbe and in the host cells, associated with early interactions between M. tuberculosis and phagocytic cells.
Comparative genomics offers a highly innovative opportunity to decipher M. tuberculosis interactions with the immune system, using transcriptional profiling approaches. In particular, early interactions between M. tuberculosis and host phagocytes, namely macrophages (Mf) and dendritic cells (DC), are thought to play a crucial role in mounting a protective immune response, and in determining the outcome of infection. Microarrays will be used to simultaneously study the entire expressed genomes of both the mammalian host and the microbial parasite during their interaction. Data analysis of the M. tuberculosis arrays, developed by the participants, will reveal patterns of the induced gene expression and most likely, unique novel targets for vaccine design. Data analysis of human arrays (GeneChips by Affymetrix) of M. tuberculosis infected monocytes and dendritic cells will allow us to identify molecular markers and pathways associated with protection. This project fully integrates the activities of internationally recognized groups that have pioneered immuno-genomics of DC and Mf with groups that have developed the TB field and M. tuberculosis arrays.
These groups will provide a new European resource, a transcriptional TB database, a key tool for the identification of new molecular markers and targets.

Call for proposal

FP6-2003-LIFESCIHEALTH-3
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Coordinator

UNIVERSITY OF MILANO-BICOCCA
Address
Piazza Dell'ateneo Nuovo, 1
Milano
Italy

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Participants (4)

INSTITUT PASTEUR
France
Address
28, Rue Du Dr. Roux
Paris

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ROYAL VETERINARY COLLEGE
United Kingdom
Address
Royal College Street
London

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ST GEORGE'S HOSPITAL MEDICAL SCHOOL
United Kingdom
Address
Cranmer Terrace
London

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SEKMED S.R.L.
Italy
Address
Corso Magenta 31
Milan

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