Hypoxia and the mechanisms regulating inflammatory tissue destruction in tuberculosis

点击翻译按钮获取中文摘要

Tuberculosis is a major health problem worldwide with 2 million deaths annually. There are 8,000 new cases each year in the UK and it has been specifically targeted by the Chief Medical Officer as a priority area to tackle. Worldwide, the rise of drug resistance and the long duration of therapy necessary to cure patients (minimum 6 months) means that new approaches are necessary. This requires better understanding of how disease progresses in patients. Much clinical disease is not due to the TB bug but to the body‘s inflammatory response to infection. This leads to tissue destruction which is driven by enzymes called MMPs. There has been much study of MMPs in human cells infected with tuberculosis. However, in patients, inflammation and infection will lead to a situation where the oxygen in tissues is used up. Almost nothing is known about the level to which the oxygen sinks in tissues or how this may affect MMPs and tissue destruction. This project will use tracers and scans to determine the level of oxygen in tuberculosis patients and then investigate the effect such reduced oxygen has on the control of MMP production both in human model systems and in patient tissue.