Investigating NETosis-Associated Proteins in Human TB Granulomas as Targets for Host-Directed Therapies and Prediction of Disease Progression

Mohlopheni Marakalala of the Africa Health Research Institute in South Africa will study the role of specific proteins associated with immune cell death in tuberculosis patients to better understand how the disease progresses and help develop new diagnostics and therapies. Tuberculosis (TB) is a bacterial disease that causes 1.5 million deaths per year, mostly in poor countries. Understanding how the human immune system responds to TB infection could help develop more effective, host-targeted treatments. Granulomas - tissues that form as a result of inflammation - are commonly seen in the lungs of TB patients. Their characteristics change as the disease progresses and they can cause severe lung damage. Granulomas are thought to be formed by the death of white blood cells called neutrophils, which are also abundant in the airways of patients. He will study granulomas isolated from patients at different stages of the disease to identify proteins linked to neutrophil cell death and see if they are linked with lung damage and disease progression. He will then determine whether the levels of these proteins in the blood can be used as disease biomarkers for the early detection of TB. Lastly, he will use molecular genetic techniques to reduce the level of these proteins in neutrophils and evaluate the effect on TB infection to see if the approach could be exploited as a potential therapy.