Recurrent infections with opportunistic pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia are a major cause of lung disease and mortality in cystic fibrosis patients. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), which have long been associated with epithelial cell dysfunction and more recently with defective innate immunity. However, little is known about the impact of these mutations on adaptive immunity and resulting clearance of pathogens in the lung. In light of recent evidence of CFTR function in macrophage endosomal acidification and bacterial killing, we hypothesise a further role for CFTR in antigen processing and presentation of peptide epitopes to Th cells. Antigen-presenting cells were generated from murine bone marrow and human peripheral blood and CFTR expression was demonstrated in macrophages and for the first time in dendritic cells by western blotting. Pseudomonas and Burkholderia specific CD4+ T cell hybridomas were generated as a tool to investigate antigen presentation in the presence of small molecule CFTR inhibitors. Our preliminary findings indicate an unexpected role for CFTR in antigen presentation suggesting an influence on peptide loading onto MHCII. In addition, we are investigating the influence of CFTR on antigen processing. It is tantalising to suggest a role for CFTR in presentation of bacterial antigens to Th cells through control of endosomal pH or in peptide presentation on MHCII at the cell surface. Consequently, mutations in CFTR may lead to abrogated T cell immunity as an additional novel explanation for susceptibility to infection in CF patients.
|Publication status||Published - Dec 2014|
|Event||BSI 2014 - Brighton, UK|
Duration: 1 Dec 2014 → …
|Period||1/12/14 → …|