Tuberculosis Research Unit
Professor Ajit Lalvani, Head of Group
Tuberculosis: General Background
Tuberculosis is a long-standing world-wide epidemic with 8-10 million cases a year, 2-3 million of which are fatal.
In Britain, the incidence of tuberculosis has increased progressively over the last 15 years and almost half the nation’s tuberculosis burden is carried by Londoners. Better tuberculosis control is therefore a strategic imperative globally as well as locally and has been identified as a priority by the strategic health authority. The epidemic is expanding, fuelled by the spread of HIV.
Our tools for diagnosis and prevention, now over 80 years old, are inadequate.
Tuberculosis Research Unit
Professor Ajit Lalvani and members of his group
We aim to understand how the host immune response shapes the wide range of clinical outcomes following exposure to M. tuberculosis, and to translate our research findings from bench to bedside to deliver practical solutions to improve clinical management of tuberculosis patients and tuberculosis control at the global level. The Group’s core activities are in human cellular immunology, cell biology, mycobacteriology, human genetics and epidemiology. The Group is led by clinician-scientist Professor Lalvani, who was recently recruited from Oxford to a new Chair in Infectious Diseases at Imperial College London to help Imperial in its mission to become the world's leading centre for tuberculosis research. The relocation of Professor Lalvani’s Group to the Wright-Fleming Institute at St Mary’s Campus will enable it to benefit from close involvement in London’s busiest tuberculosis and HIV clinics, and the state-of-the-art flow cytometry, confocal microscopy and biosafety category 3 containment facilities in the Wright-Fleming Institute. The Tuberculosis Immunology Group is funded by The Wellcome Trust and Imperial College Healthcare NHS Trust and is currently expanding; once recruitment is complete, it will comprise of about 10 members, including post-doctoral scientists, clinical training fellows, research students, research nurses and research assistants. The Group has several major international collaborations in Italy, Germany, USA, India, Turkey, Zimbabwe and South Africa.
Tuberculosis Research Unit: Scientific
Although tuberculous disease is common, symptom-free tuberculosis infection and exposure to tuberculosis are even more common, but only a minority of people exposed to the bacterium actually develop disease. The host response plays a critical role at each stage in the natural history of tuberculosis. Our overall goal is to dissect out components of the immune response that contribute to successful outcomes at 3 pivotal control points in the pathway from exposure to tuberculosis to disease. We will identify innate immune system genes associated with resistance to infection through a candidate-gene case-control study in well-defined cohorts with known tuberculosis exposure. A proportion of tuberculosis contacts may have transient, resolving asymptomatic infection. We will characterise the systemic and pulmonary cellular immune responses that underlie this phenomenon in humans and in the bovine challenge model. Through longitudinal analysis of ex vivo antigen-specific T-cell responses in cohorts with latent tuberculosis infection at high-risk of progression, we will define immunological profiles associated with long-term control versus responses that predict progression to active disease. The reduced risk of tuberculosis in HIV co-infection after antiretroviral therapy provides a window on partial reconstitution of protective immunity to tuberculosis. We will exploit this model to examine the extent of quantitative and qualitative reconstitution of M. tuberculosis antigen-specific immunity during antiretroviral therapy.
