MRC PhD students
 Level of study: PhD
Title of Research Project: The role of tumor necrosis factor alpha in the host protective immune response against tuberculosis meningitis
Tuberculosis (TB) is an infectious disease that is caused by Mycobacterium tuberculosis and is the most cause of mortality world wide. M. tuberculosis can infect different parts of the body.
Tuberculous meningitis (TBM) is a disease due to secondary infection of organs as a result of the haematogenous spread of TB and is the severest form of infection with M. tuberculosis. TBM develops within 6 months of primary infection. It causes death or severely disables more than half of the patients despite anti-TB treatment. TBM is more prevalent in children and HIV-infected patients.
Tumor necrosis factor alpha (TNF-a) is a cytokine that is believed to play various roles in immune and pathological responses to TB. An infection by M. tuberculosis stimulate TNF-a production by macrophages by activating toll-like receptors, and can also be expressed by activated NK cells, B cells and T cells. TNF-a is required in controlling the acute infection by M. tuberculosis.
Diagnosis of TBM is often difficult as clinical features of TBM mimic those of other chronic meningoencephalitides, so diagnosis may be presumptive, after excluding other conditions.
Understanding of the events following infection of the meningitis by M. tuberculosis is crucial as this will allow a larger platform for designing the more effective diagnostic methods.
Specific aims of the project are
TNF-a has shown to play an important role in pulmonary TB; we want to look at the role in extra-pulmonary TB.
- Establish a murine model of tuberculous meningitis using a stereotaxic device, a minimally-invasive form of surgical intervention which makes use of a three-dimensional coordinates (x,y and z planes) system to locate small targets inside the body. This will allow infection with high precision across the different groups of mice used.
- Investigate the importance of TNF signaling in protective immunity against the virulent and non-virulent mycobacterial challenge. This will be achieved by the use of wild-type and TNF knockout strains. Different parameters including Cellular infiltration, Bacilli burden Cytokine/Chemokine profiles will be assessed.
This will be accomplished in the setting of existing at the University of Cape Town in the Institute of Infectious Diseases and Molecular Medicine (Division of Immunology), the Animal Facility (with a P3 facility fitted with bio-hazard hoods of standard) and with the assistance of Ass. Prof. Lauriston Kellaway from the Department of Human Biology.
Supervisor: Dr Muazzam Jacobs, MRC Unit: Immunology and Infectious Diseases
Study Institution: University of Cape Town |
