Summary

The bacteria Streptococcus pneumoniae, also called the pneumococcus, commonly lives at the back of the nose without causing any problems. However, sometimes it infects the lungs and causes pneumonia, into the blood causing sepsis, or into the brain causing meningitis. These diseases kill over 800,000 people every year, mainly children under 5 years and adults above 65 years. In order to cause disease, the pneumococcus needs to cross the lining of the nose, which consists of special cells called epithelial cells that act as the first line of defence and form a protective barrier against infections. This research project is aimed at understanding how epithelial cells respond to and protect against pneumococcal infection that prevents this common passenger from becoming a dangerous invader.

We have introduced pneumococcus into the noses of healthy volunteers and shown that the epithelial cells help to control the infection. However, experiments using volunteers are difficult and complex because of sample availability and variations in sample quality and quantity. We will use a state-of-the-art lung-on-a-chip model developed at Southampton to study the role of epithelial cells in pneumococcal infection. This model provides a unique opportunity to grow epithelial cells that mimic real life and allow us to take real-time measurements that cannot be achieved in standard static lab experiments. We will measure how many pneumococci adhere, invade and travel across the epithelial cells. We will study how the epithelial cells respond in terms of maintaining the protective barrier and how they trigger other cells involved in the body’s immune system to clear the infection.

We expect to discover new ways in which epithelial cells respond to pneumococcal infection which may also be important for other respiratory infections. The results will provide the groundwork for extending the model to include other cells that are important in protecting us from pneumococcal disease.