516202

COPD exacerbations are a major cause of mortality and are commonly triggered by viruses. The severity of viral exacerbations is determined by the airway immune response and modulated by secondary bacterial infection. In COPD macrophages have defective phagocytic ability contributing to exacerbation susceptibility; the mechanisms underlying this are unclear. Exosomes are novel intercellular signalling vessels transporting cargo such as microRNAs to target cells leading to modified function. Their composition and abundance alters in response to infection and they are capable of macrophage regulation. I hypothesise that aberrant exosome signalling in COPD causes macrophage dysfunction resulting in exacerbation susceptibility. Using cross-disciplinary collaboration, I will compare the differences in airway-derived exosomes and their relationship with macrophage function in COPD and health. Using an ex-vivo model I will investigate the differences in epithelial exosome production in response to viral infection. Furthermore I will evaluate the effects of these exosomes on naïve macrophages and identify the altered molecular pathways contributing to the abnormal phenotype in COPD. Ultimately, I aim to discover a novel mechanism for macrophage dysfunction in COPD and increase understanding of macrophage modulation. This work could identify unique therapeutic targets to reduce immune vulnerability in COPD.