CCR5 receptor discovery could help fight against tuberculosis, HIV

A key aspect of how the body kicks the immune system into action against tuberculosis is revealed in research published today.

The authors, writing in Science, hope that their research could aid the development of novel vaccines and immunotherapies to combat TB, which is responsible for two million deaths each year.

The cause of TB is a slow-growing bacterium known as Mycobacterium tuberculosis. Scientists have known for some time that when host cells are invaded by this bacterium, the host cells are able to call up additional immune cells such as lymphocytes to fight them and try to limit the damage which the bacteria can cause.

The new research, by scientists from Imperial College London, the Universities of Cambridge and Oxford, and other international institutions, identifies a receptor on the host cells which triggers the immune cells' response to tuberculosis. The scientists demonstrated that without this receptor, known as CCR5, mycobacteria were able to thrive inside host cells, as the immune cells did not receive the signal from CCR5 to attack them.

The scientists hope that their findings could enable a novel vaccine or immunotherapy to be developed which could artificially kick the immune cells into action in the same way as CCR5. This could boost the immune response to TB.

Both types of interventions are urgently required, since the BCG vaccine does not offer optimal protection and the current treatment regimens for tuberculosis require at least 6 months medication. This encourages the development of multi-drug resistant strains, as patients often do not complete the full course of treatment.

Dr Beate Kampmann, from the Wellcome Trust Centre for Clinical Tropical Medicine and the Department of Paediatrics at Imperial College London, and one of the authors of the study, said: "These results describe a novel mechanism whereby Mycobacterium tuberculosis communicates with the human immune system. Another piece of this complex jigsaw has been filled in, which will help us to target TB with very specific drugs or vaccines.

"We can now test potential vaccines or drug candidates for the desired effect, as we understand better how they should act," adds Dr Kampmann.

The scientists believe their research will also be of interest to those developing new drugs to combat HIV, which work by inhibiting the CCR5 receptor, which plays an important role in HIV-infection. The new research suggests that such drugs could impair the ability to fight off TB in HIV-infected patients receiving CCR5 receptor antagonists. TB is a big problem for individuals with HIV, as their weakened immune system renders them highly susceptible to this disease.

This research was funded by the Wellcome Trust, the UK Medical Research Council and the Swiss National Science Foundation. It was carried out by scientists from Imperial College London, UK; the University of Cambridge, UK; the University of Oxford, UK; National University of Singapore; Nanyang Technological University, Singapore; the University of Basel, Switzerland; and Lionex Diagnostics and Therapeutics GmbH, Germany.