Regulation of TLR function: implications for the immune response in sepsis.

This project intends to study the cellular and molecular mechanisms regulating immune responses in sepsis.
We plan to combine imaging, mouse models and cell biology techniques to uncover the non-classical functions of the lipid-presenting molecule CD1, its role in the modulation of TLR function and ultimately in the outcome of immune responses during sepsis.
Each year in the UK more than 100,000 people are admitted to hospital with sepsis and around 40% of them will die as a result of the condition. A septic process starts originally with a response to an infection that leads to systemic inflammation and may result in injury of tissues and organs. Despite its high morbidity treatments are scarce and the mechanisms underlying the immune response during sepsis are not well defined. Toll-like receptors (TLRs) are pattern recognition receptors present on many immune cells that play a fundamental role in sensing microbial invasion and ultimately regulate the outcome of immune responses to the invading microbe. There is increasing evidence that TLRs play a vital role in the immune response during sepsis although the mechanisms that regulate their function are not fully elucidated.