Characterising the cellular immunity and metabolic response to Mycobacterium tuberculosis and Burkholderia pseudomallei in Indian patients for vaccine design
Led by Prof Chiranjay Mukhopadhyay (Manipal Academy of Higher Education, India), with Prof Susanna Dunachie (University of Oxford, UK) and Prof Mitali Chatterjee (IPGMER, India)
No vaccine is available for the neglected tropical disease melioidosis, and there is need of an improved vaccine for tuberculosis (TB). Both diseases are similar in that the bacteria live inside cells and their defence mechanisms are comparable. People suffering from diabetes mellitus (DM) have a three-fold higher risk of falling sick because of TB, and a twelve-fold higher risk of falling sick because of melioidosis than non-diabetic people. We therefore need to understand the reason why diabetic people are more susceptible to these bacteria. Likewise, understanding the response from the immune system of diabetic patients suffering from TB or melioidosis, will help in developing a new or improved vaccine.
We will combine expertise at the Department of Microbioloy at the Manipal Academy of Higher Education (MAHE) in India and the University of Oxford, to establish how the metabolic status of immune cells differ in diabetic people that makes them susceptible to TB and melioidosis. In particular, we will investigate the metabolism of immune cells of these patient groups. Just like every other cell in the human body, immune cells need energy to function, especially when they have to be very active, as during an infection when they have to 'fight' the pathogen. Immune cells mostly use sugar (glucose) to acquire their energy, but the cells can use different pathways to convert glucose into energy. We will investigate how the metabolism of immune cells of diabetic patients responds to an infection with TB and melioidosis and if this differs from non-diabetics. We believe this will help to design better vaccines for TB and melioidosis in people with diabetes, allow development of better immune correlates of protection, and can also help us develop ways to use medicines at the time of vaccination to boost immune responses in people with diabetes.