Defining the innate-like mucosal T-cell response to bacterial infection in airways disease

Asthma affects 350 million people globally, inflicting morbidity, mortality and massive economic costs, predominantly from infections which exacerbate airways inflammation. Long-term macrolide antibiotics reduce exacerbations but exactly how is unknown. Furthermore, the use of macrolides risks inducing antimicrobial resistance. 

I aim to elucidate how macrolides prevent exacerbations and explore the role of airway mucosal associated invariant T (MAIT) cells using three approaches. We will infect human airway samples in the laboratory. We will study long-term Haemophilus infections and synthetic MAIT-cell ligands in susceptible mice and we will then confirm these findings in humans using bronchoscopies in volunteers with asthma who are receiving macrolides. 

These studies will allow us to define who should receive macrolides and identify alternative therapies, which could help reserve macrolides for other uses. If boosting MAIT cells with synthetic ligands is effective, it could lead to the development of improved vaccines for a wide range of lung infections, which cause 6% of global human disease.