Development of in vitro models to study bacterial interactions with lymphoid tissue-associated epithelial cells

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Many bacteria are found in the noses and throats of healthy individuals, but some bacteria such as meningococci, haemophilus and moraxella can cause serious diseases ranging from localised ear, throat and lung infections to widespread blood and brain infections (septicaemia and meningitis). They can affect both the young and the old. Although some vaccines to prevent infections caused by different strains of these bacteria are available, there is still a need for vaccines to prevent infections caused by the remaining problematic bacteria such as group B meningococci, some haemophilus species and moraxella strains. To identify effective vaccine candidates, we need to identify basic mechanisms by which bacteria cause disease. Several investigators have examined how the bacteria attach to and invade human cells lining the throat (epithelial cells) by using isolated cells grown in laboratory cultures. However, increasing numbers of studies have shown that the cells that the bacteria colonise, especially around the tonsils in the throat, possess different properties to those grown under simple laboratory culture conditions. In this study, we propose to use complex culturing methods to mimic the environment that epithelial cells experience in the body. These cellular models will help us to understand better the bacterial and host components that are involved in attachment and invasion by the pathogens. Such model systems also have a wider application for studies on other pathogens. The more complete knowledge of the precise mechanisms that underlie the processes of human barrier penetration is expected to generate information that will allow us to produce better therapeutic and other intervention / prevention strategies against respiratory tract pathogens.