LATE-BREAKING ABSTRACT: Airway recruitment and anti-viral function of dendritic cells in asthmatic patients during RV-16 infection

Background Rhinoviruses (RV) are the major cause of asthma exacerbations, with asthmatics experiencing more frequent and severe infections compared to healthy individuals. This may be due to impaired (IFN) in the lower airways. Dendritic cells (DC) mediate viral recognition and plasmacytoid (p)DCs are the main producers of IFN-α. We aimed to assess whether airway recruitment of DCs is altered is asthmatic patients during RV-16 infection, and whether their anti-viral function is impaired. Methods Moderately-severe atopic asthmatics and healthy controls were infected with RV-16. Bronchoalveolar lavage (BAL) was collected at baseline, day 3 and day 8 post infection and DCs isolated using fluorescence activated cell sorting (FACS). The production of type I and III IFNs were assessed in blood pDCs following ex vivo RV-16 stimulation using ELISA. Results Type I cDCs, which cross prime CD8 + T cells and produce IFN, were significantly reduced in the BAL of asthmatics compared to healthy controls at baseline and during infection, which was associated with reduced FEV 1 during infection. IFN-α production from blood pDCs was significantly impaired in asthmatic patients following ex vivo RV-16 stimulation, correlating with baseline PC20 and change in FEV 1 post infection. Furthermore, expression of FceR1α on BAL pDCs was significantly increased in asthmatic patients, suggesting a reduced capacity to produce IFN in the airways. Conclusions The reduced anti-viral DC responses following RV-16 infection is associated with worse lung function and could allow for the more permissive respiratory viral infection observed in asthmatic patients.