Immuno-modulation by Mycobacterial Lipids and Glycoconjugates

Our main objective is to decipher the molecular cross-talk that establishes between Mycobacterium tuberculosis and host immune cells during infection. We focus on understanding the role and the structure-function relationships of cell envelope lipids and glycoconjugates in innate immune recognition of mycobacteria and stimulation of CD1-restricted T cells. 

We combine multidisciplinary approaches to decipher and exploit the immunomodulatory properties of Mycobacterium tuberculosis lipids and glycoconjugates.

We use a multidisciplinary approach combining lipidomics, microbiology, cell biology and animal experimentation to explore at the molecular level several facets of the host-pathogen interaction. Moreover, we wish to translate this fundamental knowledge into new therapeutic, preventive or diagnostic strategies/tools to be explored.

Modulation of innate immune responses 
Mycobacterium tuberculosis (Mtb) inhibits innate immune responses, including inflammation and autophagy, thus favoring its survival inside the infected host. Our goals are to uncover the molecular bases of Mtb recognition by pattern-recognition receptors, including TLRs and C-type lectins, and to identify Mtb factors that modulate macrophage function. Moreover, we wish to characterize Mt lipid trafficking within extracellular vesicles and the remodeling of Mtb lipidome during infection.

Glycolipid antigen presentation to CD1-restricted T cells
Lipids and glycolipids are important antigens that induce CD1-restricted T cell-mediated specific immune responses. We intend to define the repertoire of Mtb lipid T cell epitopes, to characterize the molecular steps and mechanisms of their presentation by antigen-presenting cells and to evaluate of the protective efficacy of these antigenic lipids in animal models of Mtb infection.

Structural and functional definitions of Mtb glycoproteome
We previously evidenced that protein-O-mannosylation is crucial for virulence of Mtb. Our aims are to identify and decipher the roles of the mannoproteins contributing to Mtb persistence, in vivo, and to understand the structure/function relationships of protein-O-mannosyl transferase in order to guide inhibition strategies.

Team members

Research Scientists

Emeline Fabre (University)
Martine Gilleron (CNRS) 
Emilie Layre (CNRS)
Jérôme Nigou (CNRS)
Michel Rivière (CNRS)
Alain Vercellone (University)
Isabelle Vergne (CNRS)

Research Engineers

Florian Boullée
Sébastien Nicolas
Sophie Zuberogoitia (CNRS)

PhD Students

Sonia Belkai
Tamara Mičková
Héctor Mayoral Reyes
Chloé Rivière

Our research topics

Viljoen et al. (2023) Nanoscale clustering of mycobacterial ligands and DC-SIGN host receptors are key determinants for pathogen recognition. Sci Adv

Mosquera-Restrepo et al. (2022) A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection. Nat Commun

Blanc et al. (2017) Mycobacterium tuberculosis inhibits human innate immune responses via the production of TLR2 antagonist glycolipids. Proc Natl Acad Sci USA

Decout et al. (2017) Rational design of adjuvants targeting the C-type lectin Mincle. Proc Natl Acad Sci USA

Gilleron et al. (2016) Lysosomal lipases PLRP2 and LPLA2 process mycobacterial multiacylated lipid antigens and generate T cell stimulatory antigens. Cell Chem Biol

Liu, Tonini et al. (2013) Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosisProc Natl Acad Sci USA

Extracellular vesicles shuttle mycobacterial immunomodulatory lipids toward bystander macrophages. CFSE-labeled M. bovis BCG extracellular vesicles (green), labeled BMDM: nucleus (blue), actin network (red). © Pierre Boyer, Elodie Vega, Antonio Peixoto, Emilie Layre, Jérôme Nigou│IPBS│CNRS/UPS