The main goal of our research group is to better understand host-pathogen interactions in tuberculosis on the molecular and cellular levels, from the discovery of novel virulence genes in M. tuberculosis to the identification of immune mechanisms involved in host defense against the pathogen, with the overall objective of proposing better strategies to control disease.
Our research aims at exploring the links between metabolism and virulence in the TB bacillus, Mycobacterium tuberculosis, and how this link was shaped throughout evolution. In particular, we use dual global gene expression profiling (RNA-seq) and transposon mutant library screening (Tn-seq) to identify genes and pathways playing a part in host-pathogen interactions in TB. We especially identified a novel mechanism of innate immune control of pathogens through zinc intoxication, and resistance strategies in pathogenic mycobacteria involving P-ATPases were discovered. We are currently deciphering the function of several P-ATPases in M. tuberculosis physiology and virulence. We also use dual RNA-seq analysis and Tn-seq analysis to understand M. tuberculosis adaptation to various host-imposed stresses, including hypoxia.
Our lab is also interested in understanding immunity to TB in absence and presence of co-infection with the AIDS virus HIV-1. In this context, we are deciphering the role of innate receptors, in particular C-type lectins, and host cell-expressed glycans in anti-mycobacterial immunity. As an example, we recently found that the C-type lectin DCIR modulates immunity to TB by sustaining type I interferon signaling in dendritic cells. The molecular mechanisms involved in DCIR signaling are being deciphered through biochemical and (phospho)proteomic experiments.
We are also exploring the role played by lymphocytes and innate lymphoid cells (ILCs) in immunity to TB. The contribution of ILCs to the immune response against M. tuberculosis is poorly known and our recent data indicate that TB infection induces some metabolism-driven phenotypic plasticity in the ILC compartment conferring an early protection against M. tuberculosis. Regarding other lymphocytes, we are currently developing imaging and functional approaches to understand which subpopulations of T lymphocytes have the best access, interaction and functional properties to reach M. tuberculosis infected cells.
Finally, in the context of TB/HIV co-infection, a predominant hypothesis to explain exacerbation of HIV-1 infection is that infection of macrophages by M. tuberculosis modulates the local inflammatory environments in favor of HIV-1 replication. We are currently exploiting different in vitro approaches to mimic this “bystander” effect emanating from sites of M. tuberculosis infection to dissect the molecular and cellular mechanisms rendering human monocytes and macrophages susceptible to HIV-1 infection. In parallel, within the context of co-infection in vivo, we establish crucial correlations of our in vitro findings in pulmonary lesions of non-human primates and human samples, including sera and pleural effusion fluid. Altogether, our ultimate goal is to deliver novel targets for diagnostic and therapeutic potential against co-morbidity established between AIDS and TB.
Claude Gutierrez (University)
Denis Hudrisier (University)
Fabien Letisse (University)
Geanncarlo Lugo (CNRS)
Olivier Neyrolles (CNRS)
Yannick Poquet (University)
Yoann Rombouts (CNRS)
Florence Levillain (CNRS)
Wendy Le Mouellic
Our research projects
Boudehen*, Faucher* et al. (2022) Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms. Nat Commun
Corral et al. (2022) ILC precursors differentiate into metabolically distinct ILC1-like cells during Mycobacterium tuberculosis infection. Cell Rep
Souriant et al. (2019) Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages. Cell Rep
Troegeler et al. (2017) C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. Proc Natl Acad Sci USA
Freire*, Gutierrez* et al. (2019) An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death. Mol Cell
Levillain*, Poquet* et al. (2017) Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation. PLOS Pathog
Confocal microscopy imaging of functional membrane micro domains (blue) in Mycobacterium tuberculosis © Y.-M. Boudehen
October 2021 – Olivier Neyrolles is awarded the CNRS silver medal. Read more… (in French)
November 2020 – Olivier Neyrolles is awarded the Jacques Piraud Prize from the Fondation pour la Recherche Médicale.
October 2018 – The 2018 PEPS Prize for Pedagogical Innovation is awarded to the IMMUNOVA project (Active, interactive and flexible learning in immunology) led by Denis Hudrisier.
The IMMUNOVA project is composed of two axes: the first is the strong use of digital resources allowing the students to prepare themselves before and after the face-to-face sessions (also available online), which provides greater flexibility and learning autonomy for all students, especially those who cannot attend classes according to established schedules; for the second axis, the students are offered to conduct team projects in immunology according to different approaches (e.g., digital resource generation, interviews with researchers, 3D printing of proteins in FabLabs, conception of serious games).
Known more about the project – Watch the video! (in French)
December 2017 – Anthony Troegeler is awarded the Bretesche Prize in medicine from the Toulouse Academy of sciences.
Anthony did his PhD studies in our lab where he worked on the role of the innate immune receptor DCIR in immunity to tuberculosis. His work was published in January 2017 in Proc Natl Acad Sci USA. He will receive the Prize on December 3 at the Hôtel d’Assézat, Toulouse.
June 2017 – Yoann Rombouts is awarded the IGO Young Glycoscientist Award 2017.
December 2016 – Olivier Neyrolles receives the Sanofi-Institut Pasteur National Junior Award in the field of neglected tropical diseases for his research into tuberculosis, during a ceremony at the Institut Pasteur, Paris. Olivier and his team contributed to understanding several aspects of the complex interactions between the tuberculosis bacillus, Mycobacterium tuberculosis, and its host, including anti-mycobacterial immunity and mycobacterial evolution, physiology and virulence…
December 2014 – Alexandre Gouzy receives the Sanofi 2014 Prize from the Toulouse Academy of Sciences.
February 2014 – Olivier Neyrolles receives the “Coup d’élan pour la Recherche Française” Prize from the Bettencourt Schueller Foundation during a ceremony at the Institut de France, Paris, in which Madame F. Bettencourt Meyers presented the Prize. This Prize rewards teams specifically chosen for the promising nature of their research programs. The Prize recognises both the quality of the work of Olivier Neyrolles’ team and the quality of the research conducted in the Tuberculosis & Infection Biology Department at IPBS in the field of vaccine and antibiotics development.
April 2012 – Hélène Botella, winner of the AXA-Academy of Sciences prize based on her work in the involvement of zinc as a natural mechanism to fight against infections.
2009 – Olivier Neyrolles receives the CNRS Bronze medal.
How the tuberculosis bacillus takes advantage of the lipids of its host
Siglec-1: Bridging the synergy between Mycobacterium tuberculosis and HIV-1
How the tuberculosis bacillus learned to respire in the absence of oxygen
A new target to fight tuberculosis: a population of immune cells favourable to the resilience of the bacillus… Press release in french
O. Neyrolles receives the “Coup d’élan pour la Recherche française” Prize from the Bettencourt Schueller Foundation (in French)