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H2020Individual fellowship2020–2024

Lac-TB · Dissecting the impact of Lactate in Tuberculosis

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-03-23 → 2024-07-27
EU contribution
€224,934
Participants
1
Scheme
MSCA-IF

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Results in brief

Dissecting the impact of Lactate in Tuberculosis

Tuberculosis (TB) is a pathogen infecting macrophages in the lung where it can persist for decades. It is a global public health challenge; in 2021, 10.6 million people fell ill with TB and 1.6 million died1, despite vaccination and available treatments. The emergence of multidrug resistant TB and new antibiotic resistance strains exacerbate disease burden. Macrophages are capable of bactericidal activity towards Mycobacterium tuberculosis (M.tb), essential for infection control. To design novel host-directed therapies, a better understanding of how M.tb infection impacts host immune responses is crucial. The overall aim of Lac-TB was to investigate the crosstalk between metabolic and immune responses in the context of M.tb-infection, with a particular focus on macrophage responses to lactate, which is an abundant compound in lungs of M.tb-infected individuals. Exploiting this knowledge could be key for the design of new TB therapies, which are an urgent, unmet need.

Data: CORDIS, © European Union

Project objective

Tuberculosis (TB) is a major global public health problem in which one-fourth of the world’s population is latently infected. Host-directed therapeutics are a promising approach; however, we require a comprehensive understanding of how host-pathogen interactions impact signalling pathways and cellular responses to dictate disease outcome.Metabolic reprogramming of immune cells has been described during Mycobacterium tuberculosis (M.tb) infection, resulting in active glycolysis and lactate production. Lactate is an active signalling molecule and macrophages, the main M.tb cell target, can respond to it through different transporters.The main aim of this project is to investigate the crosstalk between metabolic and immune responses in the context of M.tb infection, with a particular focus on macrophage responses to lactate. This project has the potential of revealing new host immune-metabolic therapeutic targets for TB disease.Birmingham has one of the highest rates of TB in the UK and University of Birmingham (UoB) is a world-reference institution for metabolic and metabolomic studies. Dr Llibre has a strong background in immunology and moving to Dr Mauro’s laboratory at UoB will provide her with a rare opportunity to obtain a unique skillset, allowing her to study cell metabolism in high resolution. The expertise, facilities and supervisory team at the host institution, together with Dr Llibre’s extensive knowledge on immunology and infectious disease ensure the feasibility of this project. UoB will provide Dr Llibre a privileged environment to fully develop all the skills required to lead a successful research group, including training in scientific communication; opportunities for supervising and teaching, for learning how to coordinate a project and protect intellectual property. At the end of the fellowship, Dr Llibre will be at the forefront of the much needed and exciting field of immuno-metabolism, equipped to secure funding as an independent researcher.

Original text from CORDIS.

Participants

Links

Data: CORDIS, © European Union