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More about our research

Our research interests follow three main themes.

Modulation of innate immune responses by mycobacteria

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M. tuberculosis is recognized by several Pattern Recognition Receptors (PRRs), including TLRs and C-type lectins, allowing its detection by the innate immune system. However, the pathogen is able to undermine innate immune responses, including inflammatory response and autophagy, thus favoring its survival inside the infected host.

Our main working axes are:

  • Molecular bases of M. tuberculosis recognition by PRRs (TLR2-1/6, DC-SIGN, Mincle, Dectin-1, Dectin-2), identification and structural characterization of M. tuberculosis ligands (PAMPs).
  • Molecular mechanisms used by Mtb to inhibit innate immune responses.
  • Rational design of synthetic analogs of mycobacterial immunomodulatory molecules with the objective of developing adjuvants or anti-inflammatory agents: mode of action and therapeutic potency.
  • Structure and function of mycobacterial cell envelope in vivo. 

Molecular bases of glycolipid antigen presentation to CD1-restricted T cells

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Lipids are important antigens that induce T cell-mediated specific immune responses. They are presented to T cells by a class of MHC-I like proteins, namely CD1. Despite the highly diverse and abundant lipid content in the mycobacterial cell envelope, only a few of these lipids have been shown to stimulate CD1-restricted T cells. We previously described that some mycobacterial glycolipid antigens must be processed, however the underlying molecular mechanisms remain poorly defined. Altogether, lipid antigen properties make them attractive for their use in subunit vaccines against Mtb.

 

Our main working axes are:

  • Characterization of the repertoire of mycobacterial lipid antigens involved in T cell responses.
  • Functional and structural studies of CD1-lipid complexes, CD1 loading lipid mechanisms and investigation of specific recognition by the TCRs.
  • Molecular mechanisms of lipid antigens processing: functional and structural studies of CD1e, definition of the repertoire of lipid-derived epitopes, characterization of lysosomal enzymatic activities involved in the generation of lipid epitopes.
  • Evaluation of lipid neoantigen protective effect in animal models challenged with M. tuberculosis and proof-of-concept that CD1-restricted T cells can protect against mycobacterial infection. 

Structural and functional definitions of M. tuberculosis glycoproteome

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Protein glycosylation is of the most abundant and biologically significant post-translational modification of proteins with considerable effects on their properties and biological activities. Protein O-mannosylation, known to be essential for fungi and animals, had been evidenced in actinobacteria, including M. tuberculosis. We have recently shown that this process is required for the virulence of M. tuberculosis.

Our main working axes are:

  • Identification of glycoproteins and definition their roles in the in vivo replication and virulence of M. tuberculosis.
  • Identification of glycosylating enzyme activity markers exploitable for setting on a high-throughput screening test for bacterial protein-O-mannosylation inhibitors of potential therapeutic value