TY - JOUR T1 - Late-breaking abstract: IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression may impair the interferon response to rhinovirus in allergic airways JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 2912 AU - Adam Collison AU - Luke Hatchwell AU - Jason Girkin AU - Kristy Parsons AU - Junyao Li AU - Jie Zhang AU - Simon Phipps AU - Darryl Knight AU - Nathan W Bartlett AU - Sebastian L Johnston AU - Paul S Foster AU - Peter A B Wark AU - Joerg Mattes Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/2912.abstract N2 - Background: Asthma exacerbations represent a significant disease burden. The most common cause of an asthma exacerbation is rhinovirus (RV) infection, which is detected by host Toll-like receptors (TLR) including TLR7. Some asthmatics have been shown to have impaired interferon (IFN) responses to RV, though the mechanism remains poorly understood.Aim: To investigate the importance of intact TLR7 signaling in-vivo using mouse models of house dust mite (HDM)-induced allergic airways disease (AAD) exacerbated by RV infection.Methods: Wildtype and TLR7-deficient (Tlr7-/-) BALB/c mice were sensitised and challenged with HDM prior to infection with RV1B. Mice received either recombinant IFN or adoptively transferred plasmacytoid dendritic cells (pDC). Infection, AAD and anti-viral responses were assessed at the peak of RV infection.Results: Allergic Tlr7-/- mice upon RV infection had impaired IFN release, increased virus replication and exaggerated eosinophilic inflammation and airways hyperreactivity (AHR). Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFN release in the absence of host TLR7 signaling. TLR7 expression in the lungs was suppressed by allergic inflammation and by IL-5 in the absence of allergy. Human subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, showed reduced TLR7 and IFN expression in biopsies. TLR7 expression inversely correlated with percentage of sputum eosinophils.Conclusions: This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression. ER -