The gut microbiota plays essential roles in regulating host biology, but the mechanisms involved remain poorly understood. The newly created team is interested in a novel molecular interaction between the immune system and the intestinal microbiota. Some bacteria produce vitamin B2 in response to oxidative stress occurring during intestinal inflammation. This vitamin B2 production results in the synthesis of metabolites which are seen as antigens by a major T lymphocyte subset called MAIT cells. Surprisingly, these non-classical antigens can travel through the host body and contribute to MAIT cell maturation in the thymus (Legoux et al, Science 2019).
The goal of this Master2 project is to explore the migratory properties of microbiota-derived antigenic metabolites. We wish to determine:
-the ability of metabolite antigens to cross the intestinal barrier in vivo in mice
-the tissue tropism once crossed the intestinal barrier
-the stability and life-span of metabolite antigens in vivo
-the impact of microbiota-derived antigens on MAIT cell function
The project will help understand how mammalian hosts interact with their intestinal microbes.
Expected profile
Curiosity and enthusiasm for science. Previous experience with mouse work would be appreciated.
Related publications
Legoux#, Bellet, Daviaud, El Morr, Darbois, Niort, Procopio, Salou, Gilet, Ryffel, Balvay, Foussier, Sarkis, El Marjou, Schmidt, Rabot and Lantz#. Microbial metabolites control thymic development of Mucosal Associated Invariant T cells. Science 2019 366: 494-499. #Co-corresponding authors.
Legoux*#, Gilet*, Procopio, Echasserieau, Bernardeau, Lantz#. Molecular mechanisms of lineage decisions in metabolite-specific T cells. Nature immunology 2019 20: 1244-1255. *Equal contribution. #Co-corresponding authors.
Salou*, Legoux*, Gilet*, Darbois, du Halgouet, Alonso, Richer, Goubet, Daviaud, Menger, Procopio, Premel, Lantz. A common transcriptomic program acquired in the thymus defines tissue-residency of MAIT and NKT subsets. Journal of Experimental Medicine 2019 216:133-151. *Equal contribution.
Lantz, Legoux. MAIT cells: programmed in the thymus to mediate immunity within tissues. Current Opinion in Immunology 2019. 58:75-82. Review.
Legoux*, Salou*, Lantz. MAIT cell development and function: the microbial connection. 2020 4:710. Immunity. Review. *Equal contribution.
Contact
François Legoux
