CNRS Research associate Emilie Layre receives grant from the ANR Young Researchers programme 2020
TB-ModuLip – Discovery of new immunomodulatory lipids of Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) is very effective in establishing a chronic infection in humans thanks to strategies to escape and modulate the host defenses. The development of new anti-TB strategies requires a better understanding of the molecular bases of this complex interplay. The lipids produced by Mtb play a key role in host-pathogen interactions, by acting as Pathogen Associated Molecular Patterns, antigens and/or virulence factors. This repertoire has been essentially characterized by studying the composition of the bacillus envelope. Despite decades of remarkable work, it is not fully uncovered. High-sensitivity lipidomic approach is now allowing studying Mtb lipid repertoire in a global way, beyond the bacillus envelope, within infected cells and extracellular vesicles released by the bacillus and by host cells. As a preamble to the TB-ModuLip project, these analyses have highlighted the existence of several uncharacterized lipid families. Likely key immunomodulatory lipids have been selected because of their selective production by virulent mycobacteria species, which include infection-specific molecules and lipids with potential long-distance effects through their shuttling by extracellular vesicles. The TB-ModuLip project aims at characterising the structure of these new lipid families, their immunomodulatory properties and their contribution to the bacillus virulence, by combining state-of-the-art biochemistry methods available at the IPBS and in vitro and in vivo bioassays. The characterisation of such lipid families may reveal new immunomodulation mechanisms and give rise to novel concepts for the development of anti-TB tools.