Manipulating macrophage bioenergetics to improve patient outcomes in TB infection

uberculosis (TB) is the most lethal infectious disease worldwide, causing 1.8 million deaths annually. For the last 4 years in Ireland, we have seen a doubling of TB cases after the use of immuno-suppressants called TNF blockers, and the emergence of drug resistant TB in Irish people for the first time in this regard. Targeting and boosting the body’s natural immune response against the bacteria that causes the disease, Mycobacterium tuberculosis (Mtb), is a key strategy to develop new treatments to overcome drug resistant strains of the disease.

Central to this natural immune response is the lung macrophage, a cell that lives inside the lungs and is the first line of defence we have against infection with Mtb. There is evidence that while some lung macrophages live their whole lives in the lung, others travel to the lung from the bloodstream when an infection is present. It is likely that these two differing populations of lung macrophages – those that are always present in the lung, and those that are attracted there due to an infection – behave in different ways and have different abilities to fight infection with Mtb. Learning more about these differences and about ways to boost the infection-fighting properties of these different types of lung macrophages will lead to new treatments for TB.

Specifically, we will be looking at the role of cell metabolism (the way different lung macrophages take in energy sources such as sugars and fats and uses them) in the ability of the lung macrophages to kill Mtb, and how we can manipulate this metabolism to enhance the lung macrophage’s killing ability in order to improve TB treatments.

Award Date
26 June 2020
Award Value
€523,127.00
Principal Investigator
Dr Laura Gleeson
Host Institution
Trinity College Dublin
Scheme
CSF 2020