Rationale
Mycobacterium tuberculosis (Mtb) infection represents a major threat to global health. Immunometabolism, an exciting new field of research, has the potential to offer novel targets for Mtb treatment and vaccination through manipulation of host macrophage response to infection and exploitation of trained immunity. However, the specific role of immunometabolism in the innate response to TB in humans has not yet been defined.
Aims and Objectives
1. We will define the role of host glucose metabolism in human alveolar macrophage function in response to Mtb infection.
2. We will investigate the impact of currently licensed metabolically targeted drugs on human alveolar macrophage glucose metabolism and function in response to Mtb infection.
3. We will describe differences in human macrophage glucose metabolism in patients with increased susceptibility to Mtb infection compared to normal controls and define the contribution of these differences to their impaired macrophage function, with the potential for generating patient-specific treatment adjuncts.
4. We will define differences in host metabolic profile in different clinical phenotypes of Mtb infection seen in TB patients in St James’s Hospital, to clarify the impact of altered cellular metabolism to overall disease phenotype, informing future development of metabolically-targeted therapies and vaccines.
Research Methodology
Patient samples will be obtained through on-site collaboration with St James’s Hospital staff, and experimental investigation of metabolic profiles and macrophage function in response to Mtb infection will be conducted and correlated with clinical data collected.
Anticipated Outcomes
The applicability of immunometabolism to Mtb infection in humans will be defined, permitting rapid translation of new discoveries in the field into novel therapeutic and vaccine adjuncts for tackling the major global health threat of TB disease.
