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Dan Corral

Biography

I obtained a Bachelor degree in Cellular Biology and Physiology at the Paul Sabatier University, Toulouse, France, in 2013. In 2016, I obtained my Master degree in Immunology and Infectious Diseases  (https://www.masterimitoulouse.fr/). During my Master degree, I did a first internship (2 months long) at the Center for Pathophysiology of Toulouse Purpan (INSERM, Toulouse, France) in the team of Dr. Daniel Dunia ( https://www.cptp.inserm.fr/en/research-teams/team-7-dunia-casper/ ) under the supervision of Dr. Cécile Malnou on “Epigenetic modifications induced by bornavirus infection on genes involved in neuronal processes”. For the 2nd internship (6 months long), I joined the team of Dr. Olivier Neyrolles at IPBS under the supervision of Pr. Denis Hudrisier on “Study of the reactivity of human MAIT in Mycobacterium tuberculosis infection”. In September 2016, I started my PhD studies in the Neyrolles lab, supervised by Pr. Denis Hudrisier, with the objective of deciphering the role of Innate Lymphoid Cells during Mycobacterium tuberculosis infection.

 

Current research project

The aim of my PhD project is to decipher the role of mucosal lymphoid cells, especially MAIT (Mucosal-Associated Invariant T cells) and Innate Lymphoid Cells (ILCs) during Mycobacterium tuberculosis infection (Mtb) in mice model.

My project is focused on ILCs that remains largely unknown in the context of Mtb. ILCs forms a group of lymphoid cells, localized preferentially at mucosal surface, like lungs. ILCs represent the innate counterpart of T CD4+ lymphocytes and classically divided in 4 groups based on their transcription factor expression and functions similar with T cell subsets : Natural Killer cells (NK), ILC1 expressing T-bet and IFN-g, ILC2 expressing GATA3 and IL-5, -9, -13 and ILC3/LTi with RORgT and IL-17, -22 expression. Several studies have highlighted a major role for these cells, through their capacity to sense the environment, in controlling the immune response with a dual role in inflammatory and repair phases. The aim of our project is to analyse the dynamics of ILCs upon Mtb infection, in the murine model and to understand their contribution to the balance between immunity-driven protection and pathology, key parameters in ensuring Mtb elimination while preserving functional integrity of the lung tissue. This project is divided in three axis :

  1. How ILCs contribute to immunity against Mtb and its consequence on physiopathology? Collaborators: Jean-Philippe Girard (IPBS, Toulouse).
  2. Which are the molecular mechanisms involved in ILCs plasticity during infection? Collaborators: Matthew Hepworth (The University of Manchester, UK, http://www.mig.manchester.ac.uk/people/matthewhepworth/ ) , Etienne Meunier (IPBS, Toulouse, France, http://www.ipbs.fr/immune-detection-and-elimination-pathogens )
  3. How sexual differences modulate the response of ILCs during infection? Collaborators: Jean-Charles Guéry (CPTP, Toulouse, France, https://www.cptp.inserm.fr/equipes-de-recherche-2/equipe-3-j-c-guery/ )

In addition to this main project, I also conducted a second project on MAIT in close collaboration with Alexia Dumas in the team working on microbiota and Mycobacterium tuberculosis. MAIT cells form a recently discovered subset of unconventional T cells with innate-like functions against cells infected with some intracellular bacteria. By their localization at mucosal surfaces like lungs, and their ability to sense inflammation in tissue, these cells could have a role in Mtb infection. We have shown in an antibiotics-treated mouse model that microbiota confers an early protection in lung of Mtb-infected mice. The dysbiosis induced by antibiotic treatment does not impair global inflammation and classical immune cells infiltration (myeloid cells, T cells, NK cells) in lung of infected-mice, but induced a significant decrease in MAIT cells accumulation in lung associated with impaired function. These results suggest that MAIT cells could contribute in the early protection against Mtb in an microbiota-dependent manner. This work was published in Frontiers Immunology in 2018 (https://www.frontiersin.org/articles/10.3389/fimmu.2018.02656/full ).