Defining host and microbe-derived immune targets for development of improved host-directed therapies and vaccines for TB

Almost one third of the world's population is infected with Mycobacterium tuberculosis (Mtb) with almost 2 million deaths to tuberculosis (TB) annually. Over 400 patients are treated for active TB annually in Ireland, with an increasing number of drug-resistant cases emerging. Currently treatment involves a multi-drug course for 6 months, which is extended to 2 years in cases of multi-drug resistant TB (MDR-TB). There is an immediate need to shorten the current TB treatment as drug compliance for this length of time is a huge problem. Furthermore the current vaccine, BCG, works with varying efficacy.
Improved drug treatments and vaccine design are urgently required. Specialised cells in the lung, called alveolar macrophages, are the first cells which the bacteria encounters and are crucial to the resolution of the disease. We need to understand how these cells responds during TB infection to develop new treatments. These cells use a number of process to get rid of unwanted invaders. Autophagy is one of the cell's mechanisms which can eliminate unwanted cargo, such as cell debris or damaged cellular components. Autophagy has also been shown to play an important role in eliminating bacteria and viruses by degrading them with acidic enzymes. The mechanism of autophagy in human alveolar macrophages during TB disease is unclear. However understanding this important immune mechanism will identify targets that can then be used to develop new drug treatments and potential vaccine candidates.
We will investigate whether drugs used to treat other diseases may be used for TB by targeting autophagy to improve the immune response of TB patients. We will also examine the bacteria to identify regions of the bacteria that are responsible for manipulating autophagy and the immune response. This study will to contribute to the development of improved treatment options for TB patients and vaccine design.

Award Date
23 October 2015
Award Value
Principal Investigator
Professor Joseph Keane
Host Institution
Trinity College Dublin
Health Research Awards