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Eptihelial-dendritic cell interplay

in the shaping of the immune response to Neisseria meningitidis and N. lactamica.

Group B Neisseria meningitidis is a human pathogen for which a universally effective vaccine is still not available. It is the cause of septicaemia and meningococcal meningitis. N. meningitidis is an opportunistic pathogen that can be carried asymptomatically in the upper respiratory tract without ever causing any disease and thus they appear to be tolerated by our defence mechanisms. One of the most intriguing questions in the study of host-bacteria interactions is how some bacteria are able to colonise mucosal surfaces for long periods of time without provoking an immune response, whilst pathogens capable of causing us harm are often quickly eliminated by the hosts’ immune response. However, for reasons that are not yet fully understood in some individuals such bacteria can cause devastating disseminated infections such as septicaemia and meningitis. Close relatives of N. meningitidis such as N. lactamica colonise the same site without ever being associated with human disease. Interestingly the majority of factors considered to be virulence factors are also present in commensal neisserial species including N. lactamica. Although certain factors found in N. meningitidis that are associated with disease are not present in N. lactamica, both bacteria have the ability to colonise the nasopharynx without being cleared by the immune system.

The first true immune cells likely to be encountered by colonising Neisseria are called dendritic cells. Dendritic cells play a critical role in initiating the immune response and they are highly sensitive to the environment within which they sit. In this study, we propose to compare the effect of both N. meningitidis and N. lactamica on the dendritic cells. Through such studies we will build a unique picture of the differences between commensal and pathogenic neisserial species and the immune modulating responses they evoke. The work will directly inform our approaches to the development of vaccines against pathogenic bacterial infections of the upper respiratory tract and to the generation of agents that can modulate the potential of these bacteria to cause disease.