The way in which bacteria that cause bacterial meningitis mimic human cells to evade the body's innate immune system has been revealed by researchers at the University of Oxford and Imperial College London.
The study, published in Nature, could lead to the development of new vaccines that give better protection against meningitis B, the strain which accounts for the vast majority of cases of the disease in the UK.
Meningitis involves an inflammation of the membranes covering the brain and the spinal cord as the result of an infection. The infection can be due to a virus or bacteria, but bacterial meningitis is much more serious with approximately 5% of cases resulting in death. The disease mainly affects infants and young children, but is also often found in teenagers and young adults. The disease is frightening because it can strike rapidly, with people becoming seriously ill within hours.
The bacterium Neisseria meningitidis is the most common cause of bacterial meningitis. It comes in different forms, causing different strains of the disease. With vaccines against strains A and C, group B now accounts for around 90% of cases in the UK. While there is still no vaccine available for strain B, two vaccine candidates are in clinical trials.
The Oxford and Imperial research team, funded by the Wellcome Trust and Medical Research Council, looked at how one protein in the outside coat of Neisseria meningitidis enables the bacteria to avoid being attacked and killed by the complement system, part of the body's innate immune system.
The complement system is designed to attack all foreign bodies that come into contact with the blood. We have particular sugar molecules on the surface of our own cells that flag them as being part of our body and stop them from being attacked and killed. This system works through factor H, a molecule that circulates in the blood and binds to the sugars on the surface of our cells, preventing any immune response.
Critically, the protein on the outside of Neisseria bacteria also binds factor H. Called factor H binding protein, it makes the bacteria appear like human cells and so prevents any attack from the innate immune system.
The researchers, led by Professor Susan M. Lea of the Sir William Dunn School of Pathology at the University of Oxford and Professor Christoph M. Tang of the Centre for Molecular Microbiology and Infection at Imperial College London, determined the structure of human factor H attached to factor H binding protein on the meningitis bacterium.
They found that the protein in the bacterial coat mimicked the sugars on the surface of human cells precisely, enabling the bacteria to bind factor H in the same way as human cells.