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Molecular markers of M. tuberculosis early interactions with host phagocytes

Final Report Summary - MM-TB (Molecular markers of M. tuberculosis early interactions with host phagocytes)

The goal of the 'Molecular markers of M. tuberculosis early interactions with host phagocytes' (MM-TB) project was 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 Mycobacterium tuberculosis and phagocytic cells.

Comparative genomics offers a highly innovative opportunity to decipher Mycobacterium tuberculosis interactions with the immune system, using transcriptional profiling approaches. In particular, early interactions between Mycobacterium 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 simultaneously study the entire expressed genomes of both the mammalian host and the microbial parasite during their interaction. Data analysis of the Mycobacterium 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 Mycobacterium tuberculosis infected monocytes and dendritic cells will allow us to identify molecular markers and pathways associated with protection.

This study provided the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. The results also underlined the extraordinary plasticity of host cell and pathogen responses to infection, and provided a solid framework to further understand the complex mechanisms involved in immunity to Mycobacterium tuberculosis and in mycobacterial adaptation to different intracellular environments.

The partners have implemented an IT-based integrated knowledge management system providing a new centralised European resource - a transcriptional TB databases. Gene regulation data for all analysed eukaryotic genes are available in the publicly available Genopolis database. Both databases are 'Minimum information about a microarray experiment' (MIAME) compliant.

Potential applications:

- 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 tuberculosis vaccine effort, specifically by enabling us to define better the sub-populations to be included in future vaccine trials.