Keywords: Immunology; vaccines; tuberculosis; mycobacteria; dendritic cells; macrophages; microarray; transcriptional profiling; database; vaccine
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 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 study simultaneously 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 mouse and human arrays (GeneChips by
Affymetrix) of M.tuberculosis-infected monocytes and dendritic cells will
allow identification of molecular markers and pathways associated with
This STREP fully integrates the activities of internationally recognised groups that have pioneered the TB field and the development of M.tuberculosis arrays with groups that have developed immuno-genomics and, in particular, transcriptional profiling analysis of phagocytic cells. These groups will implement an IT-based integrated knowledge management system providing a new centralised European resource - a transcriptional TB databases. This transcriptional profiling database should have a major impact on the identification of new molecular markers and molecular targets, and will certainly support the recent European TB vaccine effort.
Tuberculosis is a major public health problem. One third of the world population is estimated to carry latent infections, and active disease kills nearly 1.5 million individuals every year. 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. More than 14% of primary TB infections are MDR cases in several Eastern European countries. The future development of a new vaccine against TB demands a better understanding of the interactions between M.tuberculosis and the immune system of its host, as well as the identification of markers of protection against TB for an appropriate and informative follow-up on individuals included in phaseI/II vaccine trials.
In particular, early interactions between the tubercle bacillus and host phagocytes, namely macrophages and dendritic cells, are thought to play a crucial role in mounting a protective immune response, and in determining the outcome of infection (1). These antigen-presenting cells are the very first cells encountered by the bacillus during a natural infection. They present mycobacterial antigens to T lymphocytes and shape the type of immune response by secreting cytokines. Identification of signals induced by these DC and the other interacting cell populations should help to design markers of protection.
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.
We should be able to define global molecular patterns associated with protection and identify novel microbial antigens or pathways that may be targeted by future chemotherapy and vaccines.
The partners will implement an IT-based integrated knowledge management system providing a new centralised European resource - a transcriptional TB database.
This transcriptional profiling database should have a major impact on the identification of new molecular markers and molecular targets, and will certainly support the recent European TB vaccine effort, specifically by enabling us to define the sub-populations to be included in future vaccine trials better.
Department of Biotechnology and Bioscience
University of Milan-Bicocca
P.zza della Scienza 2
Tel: +39 02 6448 3559
Fax: +39 02 6448 3552
|Official Address||Other Information|
|2||Olivier Neyrolles||CNRS (URA 2172) |
Unité de Génétique Mycobactérienne
28 rue du Roux
|Tel: +33 1 45 68 88 40 |
Fax: +33 1 45 68 88 43
|3||Neil Stoker||Professor of Molecular Bacteriology |
Department of Pathology and Infectious Diseases
Royal Veterinary College
Royal College Street
UK-NW1 0TU London
|Tel: +44 20 7468 5272 |
Fax: +44 20 7468 5306
|4||Philip D Butcher |
Professor of Molecular Medical Microbiology
|Dept. Cellular & Molecular Medicine (Medical Microbiology) |
St George’s Hospital Medical School
UK-SW17 ORE London
|Tel: +44 20 8725 5721 |
Fax: +44 20 8672 0234
|5||Filippo Petralia||Sekmed S.R.L. |
Corso Magenta 31
|Tel: +39 340 233 7275 |
Fax: +39 028 621 30