Identifying meningococcal molecules that can suppress our immune defence system.

Research archive

Meningococcal bacteria (Nesseria meningitidis) cause severe and life-threatening diseases.  Meningitis is an inflammation of the membranes surrounding the brain and spinal cord and septicaemia is the blood poisoning form of the disease.  From the onset of symptoms, disease can rapidly progress and become life threatening or fatal within hours.  5 to 10% of patients die and there are long-term after effects including amputations, brain damage, epilepsy and deafness in 10 to 20% of survivors.  There are many different strains of Nesseria meningitidis, but serogroup B is the most prevalent in Ireland. The groups at greatest risk are babies and children under five years of age.  Currently, there is no vaccine to protect against this particular serogroup.

The bacteria are carried in the nose and throat of 10 to 25% of the population but only a small proportion of people exposed to the bacteria develop disease.  In these cases the bacteria overcome our immune defences and invade the body, spreading through the bloodstream and to the brain. This project aims to determine how the bacteria are able to avoid being destroyed by the immune system.

Scientists will find out whether the meningococcus produces molecules to influence the immune system.  Dendritic cells are part of the immune system, performing the role of 'sentinels' in the body, rapidly recognising and responding to infection.  When activated, these cells can trigger immune responses, including antibody production.  Antibodies produced by the immune system recognise and bind to antigens on the invading bacteria, thus destroying them.
Using dendritic cells as a model, the researchers will apply cutting-edge technologies to determine if there are currently unknown but powerful meningococcal molecules that help it to evade the immune system.   They will also study the ability of any new molecules identified to activate a second very important group of immune cells called T cells.  Some types of T cells protect against disease, while other types, called 'regulatory T cells', can suppress protective immunity.  This project will investigate whether these meningococcal molecules activate regulatory T cells that help meningococcal bacteria avoid being destroyed by the immune system.  A molecule called NarE was recently discovered in meningococcal bacteria, which is similar to toxins that cause cholera and traveller's diarrhoea.  These scientists will investigate whether NarE can activate or suppress immune responses, which could promote meningococcal disease.  Identifying meningococcal molecules that enable the bacteria to influence our immune defences will increase our understanding and may provide new targets for therapy and vaccination.