Targeting Neutrophil Recruitment in Pneumococcal Meningitis (360G-Wellcome-107311_Z_15_Z)

Streptococcus pneumoniae (Spn) is a significant cause of meningitis worldwide. It causes thedeath of 1 in 5 affected people despite antibiotic treatment and lifelong disability in 1 in 3 survivors.The immune response contributes to the damage caused by Spn meningitis, and controlling thisresponse may improve survival and reduce disability significantly.In my preliminary studies I found that Spn strongly activated immune responses in pericyte cells ofthe blood-brain barrier (BBB); this has never been described before. I will investigate how Spnactivates pericytes and if this response is specific to Spn. I also found that signals from immunecells stimulated with Spn activate the endothelial cells making up the BBB and I plan to describethe pathways involved in these responses. I will use an experimental model to test the role of thedifferent cell types and investigate whether existing drugs are able to target these processes todamp down the inflammatory response and potentially reduce nerve damage.My goal is to identify new uses for existing drugs, or potential drug targets for novel drugs, thatcould modulate the immune response in Spn meningitis and lead to better outcomes for patients